A 

TEXT-BOOK 

OF 


HISTOLOGY 


ARRANGED  UPON  AN  EMBRYOLOGICAL  BASIS 


BY 
DR.  FREDERIC  T.  LEWIS 

ASSISTANT  PROFESSOR  OF  EMBRYOLOGY  AT  THE   HARVARD  MEDICAL  SCHOOL 

AND 

DR.  PHILIPP  ST6HR 

FORMERLY  PROFESSOR  OF  ANATOMY  AT  THE  UNIVERSITY  OF  WURZBURG 


SECOND  EDITION,  WITH  495  ILLUSTRATIONS 

Being  the  Seventh  American  Edition  of  Stohr's  Histology 
From  the  Fifteenth  German  Edition,  edited  by  Dr.  O.  Schultze 


PHILADELPHIA 
P.   BLAKISTON'S  SON   &   CO. 

1012  WALNUT  STREET 


COPYRIGHT,  1913,  BY  P.  BLAKISTON'S  SON  &  Co. 


THE      M  A  T»  I,  E     PRE9S     YORK.     FA. 


PREFACE 

PHILIPP  STOHR,  whose  Lehrbuch  der  Histologie  is  here  presented  with 
many  additions  and  changes,  was  born  at  Wiirzburg,  June  13,  1849,  and 
died  in  his  native  city,  November  4,  1911.  It  was  his  good  fortune  to 
study  under  the  most  eminent  of  all  histologists,  Albert  von  Kolliker, 
whose  assistant  he  became  in  1877,  and  whom  he  succeeded  as  Professor 
of  Histology  and  Embryology  at  Wiirzburg  in  1902.  During  these  years 
he  enriched  anatomy  with  a  whole  series  of  important  contributions,  and 
he  continued  his  researches  until  the  time  of  his  death,  dealing  with  the 
relation  of  lymphocytes  to  epithelium,  the  degeneration  of  glands  in  the 
vermiform  process,  the  development  of  hairs,  the  nature  of  the  cells  of  the 
thymus,  and  many  other  subjects.  But  as  stated  by  Professor  Schultze 
in  a  memorial  address  (Verh.  phys.-med.  Ges.,  Wiirzburg,  1912,  vol.  42), 
"Stohr's  position  as  an  anatomist  doubtless  depends  upon  his  surpassing 
gifts  as  a  teacher."  He  considered  that  the  instruction  of  young  men  in  an 
intricate  science  was  worthy  of  his  best  efforts,  and  his  time  was  freely 
given  to  preparing  demonstrations,  and  to  writing  and  revising  his  Lehr- 
buch der  Histologie  und  der  mikroskopischen  Anatomie  des  Menschen. 

The  first  edition  of  the  Lehrbuch  appeared  in  1887,  and  the  fifteenth, 
edited  by  Schultze  on  the  basis  of  memoranda  which  Stohr  had  prepared, 
was  published  in  1912.  Meanwhile  the  volume  nearly  doubled  in  size. 
It  has  been  translated  into  many  languages,  including  the  Japanese,  and 
the  late  editions  have  been  issued  in  very  large  numbers.  As  principal 
characteristics  of  the  book,  there  may  be  mentioned,  first,  its  clear  and 
concise  style,  somewhat  dogmatic  because  of  the  omission  of  essentially 
all  references  to  authorities.  Since  Stohr  considered  that  adequate  refer- 
ences would  be  impossible  in  a  book  of  small  size,  he  omitted  them  alto- 
gether. Second,  the  almost  entire  absence  of  borrowed  illustrations.  As 
Schultze  remarks,  Stohr  possessed  unusual  artistic  talent,  and  many  of 
the  excellent  figures  were  drawn  by  Stohr  himself.  Third,  the  full  direc- 
tions for  the  preparation  of  every  specimen  illustrated.  In  addition  to 
these  special  characteristics,  the  book  has  the  advantages  of  being  essen- 
tially a  resume  of  Kolliker's  exhaustive  Gewebelehre,  adapted  to  the  use  of 
students. 

The  first  American  edition  of  Stohr' s  -Histology  was  edited  by  Dr. 
Alfred  Schaper,  at  that  time  Demonstrator  of  Histology  and  Embryology 


35946:; 


vi  PREFACE 

at  the  Harvard  Medical  School,  and  was  published  by  Messrs.  P.  Blakiston, 
Son  &  Co.  in  1896.  This  edition  was  essentially  a  literal  translation,  to 
which  Dr.  Schaper  added  a  chapter  on  the  placenta  and  membranes;  a 
corresponding  chapter  was  later  incorporated  in  the  German  Lehrbuch. 
In  the  four  American  editions  which  followed,  Dr.  Schaper  made  a  limited 
number  of  further  additions,  and  supplied  some  excellent  drawings  of  his 
own. 

After  the  death  of  Dr.  Schaper,  Professor  Stb'hr  generously  consented 
to  allow  more  extensive  modifications,  provided  that  he  should  not  be 
held  responsible  for  them,  as  stated  in  the  following  note: 

In  the  new  edition  of  the  American  translation  of  my  handbook  a  number  of 
additions  and  changes  have  been  made  by  the  translator  with  my  permission. 
It  is  therefore  reasonable  that  I  should  not  take  the  same  responsibility  for  the 
translation  as  for  the  text  of  the  German  original,  and  I  would  ask  those  of  my 
colleagues  who  wish  to  question  the  correctness  of  my  assertions  in  their  papers, 
to  convince  themselves,  by  making  comparisons  with  my  last  German  edition, 
that  the  paragraphs  in  question  were  written  by  me. 

(Signed)  PHILIPP  STOHR. 

At  the  suggestion  of  Professor  Minot,  the  writer  undertook  to  prepare 
the  sixth  American  edition.  Because  of  the  great  importance  of  embryo- 
logical  interpretations  in  understanding  adult  tissues,  it  was  decided  to 
arrange  the  text-book  on  an  embryological  basis,  but  this  necessitated  more 
radical  changes  than  were  originally  contemplated.  In  describing  the 
result,  Professor  Stohr  wrote  that  the  character  of  his  book  had  been  com- 
pletely changed.  "With  all  that  has  been  left  out  of  some  parts  and 
added  to  other  parts,  it  may  without  exaggeration  be  said  that  with  the 
appearance  of  this  sixth  American  edition  my  book  has  ceased  to  exist 
in  America." 

The  writer,  therefore,  must  assume  the  principal  responsibility  for 
the  book  in  its  present  form.  There  are  certain  sections,  as  those  on  hair, 
the  eye,  and  the  ear,  which  are  largely  literal  translations,  but  elsewhere 
Stohr's  text  has  been  freely  paraphrased.  Of  the  376  figures  which  illus- 
trate the  1 5th  German  edition,  275  will  be  found  in  the  following  pages; 
220  additional  figures  have  been  supplied  from  other  sources,  and  of  these 
95  are  original.  Although  the  changes  in  the  text  are  relatively  greater 
than  in  the  figures,  much  of  the  work  is  clearly  Professor  Stohr's,  and  in 
order  to  give  full  credit  for  the  part  which  has  been  retained,  this  edition 
is  published  as  of  joint  authorship.  The  changes  which  have  been  intro- 
duced are  designed  to  make  the  text-book  more  useful  in  certain  American 
schools  where  it  has  been  adopted,  and  the  nature  of  these  changes  may  be 
explained  as  follows. 

First,  the  book  has  been  arranged  on  an  embryological  basis  and  has 


PREFACE  Vll 

become  the  only  available  text-book — in  so  far  as  the  writer  is  aware — in 
which  the  development  of  each  organ  is  described  as  an  introduction  to  the 
study  of  its  microscopic  structure  in  the  adult.  This  method  of  presen- 
tation is  believed  to  be  interesting,  logical,  and  pedagogically  practicable. 
It  proceeds  from  simple  arrangements  to  those  which  are  complex,  and  it 
emphasizes  fundamental  features  in  distinction  from  those  which  are 
secondary. 

Secondly,  a  large  number  of  citations  and  references  to  original  papers, 
both  ancient  and  modern,  have  been  inserted.  Since  the  most  obvious 
facts  of  anatomy  were  observed  first  and  details  were  learned  subsequently, 
an  historical  presentation  serves  to  differentiate  between  the  important  and 
the  trivial,  being  comparable  in  this  respect  with  an  embryological  presen- 
tation. At  the  same  time  it  is  shown  that  anatomy  has  been  a  subject  of 
absorbing  interest,  and  its  possibilities  are  by  no  means  exhausted,  con- 
trary to  an  opinion  often  expressed.  Thus  in  1821,  when  Charles  Bell 
made  his  great  discoveries  concerning  nerves,  he  stated  that  scientists 
had  often  remarked  to  him — "In  your  department  we  can  hope  for  nothing 
new.  After  so  many  eminent  men  in  a  succession  of  ages  have  laboured  on 
your  subject,  no  further  discovery  can  be  expected."  Similarly,  forty 
years  later,  an  American  professor  of  anatomy  described  his  science  as 
"a  well  reaped  field";  shortly  after  this,  the  discovery  of  the  islands  in  the 
pancreas  was  announced,  and  they  constituted  an  essentially  new  and 
important  organ.  Thus  while  morphology  continues  to  be  discredited  as 
an  effete  and  superficial  science,  dealing  merely  with  shapes  and  relations, 
it  still  reveals  new  structures  in  the  human  body,  some  of  which  are  of 
obvious  significance,  whereas  others  await  explanations  by  the  physiolo- 
gists and  chemists.  In  order  that  students  may  have  an  idea  of  the  impor- 
tant work  now  being  done  by  anatomists,  references  to  a  selection  of  recent 
papers  have  been  introduced  in  this  edition.  American  publications  have 
perhaps  been  given  particular  prominence,  but  this  is  because  they  are  more 
accessible  to  the  students  for  whom  this  book  is  written. 

As  a  third  modification,  microscopic  technique  is  described  in  a  single 
chapter,  revised  by  Mr.  L.  G.  Lowrey,  now  in  charge  of  the  instruction  in 
this  subject  at  the  Harvard  Medical  School.  It  furnishes  directions  for  a 
brief  but  practical  course  in  microscopic  technique,  especially  adapted  to 
the  needs  of  medical  students. 

In  preparing  this  edition,  the  writer  has  received  valuable  assistance 
from  many  sources.  The  account  of  the  rectum  was  written  by  Dr.  F.  P. 
Johnson,  and  Professor  Huber  has  assisted  in  revising  the  description  of 
the  kidney.  The  account  of  spermatogenesis  is  based  on  specimens  made 
by  Dr.  Scammon,  and  important  illustrations  have  been  supplied  by  Pro- 
fessors Mark,  Mallory,  Minot,  and  Mall.  Numerous  crude  figures  in 
the  earlier  edition  have  been  replaced  by  excellent  drawings  made  by  Miss 


Vlll  PREFACE 

Mabel  Herford.  To  these  and  to  many  others  who  have  offered  sugges- 
tions, the  author  makes  grateful  acknowledgment.  Messrs.  P.  Blak- 
iston's  Son  &  Co.  have  supplied  several  figures  from  their  anatomical 
publications,  and  have  endeavored  to  maintain  the  high  standard  of  press 
work  which  has  characterized  previous  editions. 

FREDERIC  T.  LEWIS. 
CAMBRIDGE,  MASSACHUSETTS, 
September,  1913. 


CONTENTS 


PART  I. 

MICROSCOPIC  ANATOMY. 
I.  CYTOLOGY. 


PAGE 

I 


THE  CELL, 

Protoplasm. 

Nucleus. 

Centrosome. 

Cell  Wall. 

Form  and  Size  of  Cells. 


CYTOMORPHOSIS, 9 


VITAL  PHENOMENA, n 

Amoeboid  Motion. 
FORMATION     AND     REPRODUCTION     OF 

CELLS,     12 

Amitosis. 

Mitosis. 

Spermatogenesis. 

Oogenesis. 

Fertilization. 


II.  GENERAL  HISTOLOGY. 


HlSTOGENESIS, 35 

Segmentation   and   the    Formation 
of  the  Germ  Layers. 

The  Fundamental  Tissues. 
EPITHELIUM, 46 

Shapes  of  Epithelial  Cells  and  the 
Number  of  Layers. 

Peripheral  Differentiation. 

Processes  of  Secretion. 

The  Nature  and   Classification   of 

Glands. 
MESENCHYMAL  TISSUES 59 

Reticular  Tissue. 

Mucous  Tissue. 

Connective  Tissue. 

Adipose  Tissue. 

Tendon. 

Cartilage. 

Bone. 

Joints. 

Teeth    (including    the    Ectoderrhal 

Enamel  Organs). 
MUSCULAR  TISSUE, 113 

Smooth  Muscle. 

Skeletal  Muscle. 

Cardiac  Muscle. 


NERVOUS  TISSUE 

General  Features. 

Development  of — 
The  spinal  nerves 
The  sympathetic  system 
The  cerebral  nerves. 

Structure  of — 

Nervous  tissue 

Ganglia 

Nerves. 

Nerve  Endings. 


130 


VASCULAR  TISSUE, 

Blood  Vessels. 

General  features. 

Development. 

Capillaries. 

Arteries. 

Veins. 
The  Heart. 
Lymphatic  Vessels. 
Blood. 

Red  corpuscles. 

White  corpuscles. 

Blood  plates. 

Plasma. 
Lymph. 


163 


IX 


CONTENTS 


III.  SPECIAL  HISTOLOGY. 


BLOOD  FORMING  AND  BLOOD  DESTROY- 
ING ORGANS, 202 

Bone  Marrow. 

Lymph  Nodules  and  Lymph  Glands. 

Haemolymph  Glands. 

Spleen. 

THE  ENTODERMAL  TRACT,.  . 215 

Mouth  and  Pharynx, 215 

Development. 

Tonsils. 

Thymus. 

Thyreoid  Gland. 

Parathyreoid  Glands. 

Glbmus  Caroticum. 

Tongue. 

Oral  and  Pharyngeal  Cavities. 

Glands  of  the  Oral  Cavity. 
Digestive  Tube, 245 

Development. 

(Esophagus. 

Stomach. 

Duodenum. 

Jejunum  and  Ileum. 

Mesentery  and  Peritoneum. 

Vermiform  Process. 

Caecum  and  Colon. 

Rectum. 

Liver, 276 

Pancreas, 289 

Respiratory  Apparatus, 295 

Development. 

Larynx. 

Trachea  and  Bronchi. 

Lungs. 

Pleura. 

URINARY  ORGANS, 306 

Wolffian  Bodies  and  Wolffian  Ducts. 

Kidney. 

Renal  Pelvis  and  Ureter. 

Bladder. 

Urethra  (in  the  female). 

MALE  GENITAL  ORGANS, 326 

Development  and  General  Features. 

Testis. 

Epididymis. 

Ductus  deferens. 

Seminal  Vesicles   and  Ejaculatory 

Ducts. 

Appendices  and  Paradidymis. 
Prostate. 


MALE  GENITAL  ORGANS. — (Continued.} 
Urethra  and  Penis. 

FEMALE  GENITAL  ORGANS, 349 

Development  and  General  Features. 

Ovary. 

Uterine  Tubes. 

Uterus. 

Menstruation. 
Decidual  Membranes  of  the  Uterus 

and  Embryo. 

Development  and  General  Fea- 
tures. 
Decidua    vera,    Amnion    and 

Chorion  laeve. 
Placenta. 
Umbilical  Cord. 

Vagina  and  External    Genital  Or- 
gans. 

SKIN, 384 

Nails. 

Hair. 

Sebaceous  Glands. 

Sweat  Glands. 

Mammary  Glands. 

SUPRARENAL  GLANDS, 404 

CENTRAL  NERVOUS  SYSTEM, 409 

Spinal  Cord, 409 

Development  and  General  Fea- 
tures. 
Adult  Structure. 

Brain, 418 

Development  and  General  Fea- 
tures. 

Medulla  Oblongata. 
Cerebellum. 
Hemispheres. 
Hypophysis. 
Pineal  Body. 
Meninges. 


EYE,. 


439 


Development  and  General  Anatomy. 

Retina. 

Optic  Nerve. 

Lens. 

Vitreous  Body. 

Tunica  Vasculosa. 

Tunica  Fibrosa. 

Vessels,  Chambers,  and  Nerves. 

Eyelids. 

Lachrymal  Glands. 


CONTENTS 


EAR, 465 

Development  and  General  Anatomy. 
Sacculus,     Utriculus,     and     Semi- 
circular Ducts. 
Cochlea. 
Nerves  of  the  Labyrinth. 


XI 

PAGE 


EAR. — (Continued.) 

Vessels  of  the  Labyrinth. 
Middle  Ear. 
External  Ear. 

NOSE,.  . 


481 


PART  II. 

MICROSCOPICAL  TECHNIQUE. 
I.  THE  PREPARATION  OF  MICROSCOPICAL  SPECIMENS. 


PAGE 

FRESH  TISSUES, 487 

ISOLATION, 488 

PERMANENT  PREPARATIONS, 489 

Fixation. 

Decalcification. 
Imbedding. 

Cutting  and  Handling  Sections. 
Staining. 


PERMANENT  PREPARATIONS. — (Continued.) 
General  Stains. 
Selective  Stains. 
Clearing  and  Mounting. 


SLIDES  AND  COVER  GLASSES, 508 

INJECTIONS, 509 

SPECIAL  METHODS, 510 

II.  THE  EXAMINATION  OF  MICROSCOPICAL  SPECIMENS. 


THE  MICROSCOPE, 514 

RECONSTRUCTIONS, 516 

DRAWINGS, 518 


PART  I. 

MICROSCOPIC  ANATOMY. 


I.  CYTOLOGY. 
THE  CELL. 

Since  1838  it  has  been  known  that  all  plants  and  animals  are  composed 
of  small  structural  elements  called  cells  (Latin,  cellula;  Greek,  KVTOS). 
The  lowest  forms  of  animals  and  of  plants  are  alike  in  being  single  cells 
throughout  life.  The  more  complex  organisms  are  groups  of  cells,  which 
have  been  derived  by  process  of  repeated  division  from  a  single  cell,  the 
fertilized  ovum.  Thus  the  human  body,  which  begins  as  one  cell,  becomes 
in  the  adult  an  aggregation  of  cells  variously  modified  and  adapted  to 
perform  special  functions.  Since  the  liver  is  a  mass  of  essentially  similar 
cells,  the  problems  of  its  functional  activity  are  the  problems  of  the  func- 
tions of  a  single  one  of  its  cells.  The  diseases  of  the  liver  are  the  result  of 
changes  occurring  in  these  cells,  which  must  be  restored  to  a  normal  con- 
dition to  effect  a  cure.  As  this  is  equally  true  of  other  organs,  it  is  evident 
that  cytology,  the  science  of  cells,  is  a  basis  for  both  physiology  and 
pathology. 

A  cell  may  be  denned  as  a  structural  element  of  limited  dimensions, 
which  under  certain  conditions  can  react  to  external  stimuli  and  perform 
the  functions  of  assimilation,  growth,  and  reproduction.  Because  of 
these  possibilites  a  cell  may  be  considered  an  elementary  organism.  It  is 
described  as  a  mass  of  protoplasm  containing  a  nucleus.  A  third  element, 
the  centrosome,  is  found  in  the  cells  of  animals,  but  it  is  doubtful  whether 
it  exists  in  the  cells  of  the  higher  plants.  It  becomes  prominent  when  a 
cell  is  about  to  divide.  Some  authorities  regard  the  centrosome  as  a  tempo- 
rary structure,  which  forms  shortly  before  division  begins  and  disappears 
after  it  is  completed.  Others  consider  it  as  a  permanent  and  essential 
part  of  a  cell,  which  accordingly  consists  of  protoplasm,  nucleus,  and 
centrosome. 


HISTOLOGY 


PROTOPLASM. 

Protoplasm  is  the  living  substance  of  which  cells  are  composed.  More 
specifically  the  term  is  applied  to  this  living  substance  exclusive  of  the 
nucleus,  or  to  the  corresponding  dead  material,  provided  that  death  has 
not  changed  its  physical  properties.  It  has  been  proposed  to  substitute 
the  name  cytoplasm  for  protoplasm  in  the  restricted  and  earlier  sense  of 
the  term,  to  call  the  nuclear  substance  karyoplasm,  and  to  consider  both 
cytoplasm  and  karyoplasm  as  varieties  of  protoplasm.  Although  these 
names  are  often  employed,  the  cell  substance  apart  from  the  nucleus  is 
ordinarily  called  protoplasm. 

Protoplasm  is  a  heterogeneous  mixture  of  substances  forming  a  soft 
viscid  mass  of  slightly  alkaline  or  neutral  reaction.  ("The  terms  may 


Centrosome. 


Emulsion  structure. 


Droplet  in  emulsion. 


Nuclear  membrane. 


Linin. 


Nuclear  sap. 


Exoplasm. 


Spongioplasm. 


Hyaloplasm. 


Chromatin  cord. 


Chromatin  knot. 


Nucleolus. 


Cell  membrane. 


Fat  globule. 


Granules. 


Crystal. 


FIG.  i. — DIAGRAM  OF  A  CELL. 

In  the  four  quadrants  different  types  of   protoplasmic  structure  are  represented — namely,  homogeneous, 

granular,  foam-like,  and  fibrillar. 

be  used  interchangeably  for  an  alkalinity  which  is  so  slight" — Henderson.) 
It  is  ordinarily  more  than  three-fourths  water,  and  the  remainder  con- 
sists of  salts  and  organic  substances,  some  in  solution  and  some  in  a  colloidal 
state.  The  organic  bodies  are  classed  as  proteins,  glycogen  or  some  allied 
carbohydrates,  and  lipoid  (fat-like)  bodies.  Protoplasm  may  exist  in  a 
numberless  variety  of  forms. 

On  microscopic  examination,  even  with  lenses  of  the  highest  power, 
the  protoplasm  of  certain  living  cells  appears  homogeneous  and  structure- 
less. But  most  of  the  cells  which  the  histologist  examines  are  not  living. 


PROTOPLASM  3 

i 

They  have  been  killed  by  various  reagents,  selected  as  causing  the  most 
rapid  fixation  possible.  The  protoplasm  of  such  cells  usually  exhibits 
granules,  fibrils,  or  networks  with  closed  or  open  meshes.  Whether  these 
structures  are  wholly  due  to  precipitation  and  coagulation  is  difficult  to 
determine,  but  indications  that  they  preexist  have  been  observed  in  cer- 
tain living  cells..  In  any  case,  the  various  forms  of  coagulation  occur 
with  such  constancy  that  their  study  is  of  the  utmost  importance  to  the 
histologist. 

Even  the  ground  substance  of  protoplasm,  in  which  the  fibrils  or 
granules  are  imbedded,  is  not  necessarily  homogeneous.  According  to 
Biitschli's  interpretation  it  has  the  structure  of  foam  or  of  an  emulsion — 
that  is,  it  consists  of  minute  droplets  of  one  substance  completely  sur- 
rounded by  walls  of  another  substance.  In  these  walls,  granules  and  fila- 
ments may  be  lodged,  as  seen  at  the  margins  of  the  upper  right  quadrant 
of  Fig.  i .  The  complex  chemical  activities  of  a  cell  are  said  to  be  mani- 
festly impossible  in  any  homogeneous  mass;  but  in  such  a  heterogeneous 
medium  as  an  emulsion,  they  are  conceivable  (Alsberg).  In  other  words, 
the  vital  qualities  of  protoplasm  may  not  depend  so  much  on  hypothet- 
ical complex  and  unstable  living  molecules,  as  upon  the  interaction  of  vari- 
ous substances,  made  possible  by  their  arrangement  in  droplets  and  invest- 
ing films. 

The  various  structures  commonly  observed  in  protoplasm  may  be 
grouped  as  follows: 

i.  Granules.  Ultra-microscopic  granules  doubtless  exist  in  proto- 
plasm, since  the  smallest  of  those  observed  approach  the  limit  of  visibility. 
The  minute  granules,  if  abundant,  give  the 

i  -i  Nissl's  bodies. 

protoplasm  a  dark  color.  Often  they  are  absent 
from  the  peripheral  layer  of  protoplasm,  or 
exoplasm,  which  is  then  clear,  somewhat  firmer, 
and  chemically  different  from  the  inner  endo- 
plasm  (Fig.  i).  In  addition  to  minute  granules 
such  as  may  be  found  in  most  preserved  proto- 
plasm, certain  cells  contain  larger  granules, 
which  are  important  secretory  products  elabo- 
rated by  the  cell.  In  active  gland  cells  these 
granules  are  well  defined  and  abundant,  and  FIG.  2.— CLUMPS  OF"GRANULES 
they  diminish  as  the  cell  becomes  exhausted.  ISSL'S  W IN  A  NERVE 
Various  forms  of  white  blood  corpuscles  may 

be  distinguished  by  the  size  and  staining  reaction  of  the  granules  im- 
bedded in  their  protoplasm.  In  certain  nerve  cells  (Fig.  2)  granules 
occur  in  large  groups,  known  as  NissPs  bodies.  As  Crile  has  shown, 
these  become  disorganized  as  a  result  of  surgical  shock  or  muscular 


HISTOLOGY 


fatigue.     It  is  evident,  therefore,  that  the  careful  observation  of  proto- 
plasmic granules  is  of  very  great  importance. 


FIG.  3. — 'FIBRILS  IN  A  NERVE  CELL. 


FIG.  4. — -VACUOLES  IN  A  YOUNG 
FAT  CELL. 


Nucleus. 


Reticular  apparatus. 
PIG.   6.—  RETICULAR   NETWORK    (Fig.  3). 
IN  A  NERVE  CELL.     (After 

Vacuoles. 


2.  Fibrils.  Protoplasm  may  be  permeated 
with  a  delicate  mesh  work  of  fibrils,  which  collec- 
tively constitute  the  spongioplasm,  or  filar  mass. 
This  is  imbedded  in  the  clear  hyaloplasm,  or 
interfilar  mass  (Fig.  i).  In  certain  cells  there  are 
filaments,  known  as  mitochondria,  which  are 
formed  by  the  coalescence  of  rows  of  granules. 
The  relation  between  these  structures  and  the 
reagents  used  is  discussed  by  Kingsbury  (Anat. 
Rec.,  1912,  vol.  6,  pp.  39-52).  The  spongioplasm 
may  form  an  irregular  network,  or  its  constituent 
fibrils  may  be  parallel,  passing  from  one  end  of 
the  cell  to  the  other.  In  oblique  and  transverse 
sections  of  such  cells,  the  filaments  are  cut  across, 
so  that  they  appear  as  short  rods,  or  even  as 
granules.  Fibrils  may  be  extremely  slender,  as  in 
the  case  of  those  which  radiate  through  the  proto- 
plasm at  the  time  when  the  cell  divides;  or  they 
may  be  quite  coarse,  like  the  permanent  fibrils 
characteristic  of  certain  muscle  and  nerve  cells 


__  . 

3.  acuoes.  Protoplasm  often  contains  large 
or  small  drops  of  clear  fluid,  fat,  or  some  other 
substance  less  highly  organized  than  the  surround- 
ing material  (Fig.  4).  In  preserved  cells  the 
spaces  which  were  occupied  by  these  droplets  ap- 
pear clear  and  empty,  and  are  known  as  vacuoles. 
l  Tliey  varv  greatly  in  size,  and  one  or  several  of 

them  may  be  found  in  a  single  cell. 
4.  Canals.     The  protoplasm  of  certain  cells  is  said  to  contain  fine  tubes 
or  clefts  which  communicate  with  lymphatic  spaces  outside  of  the  cell 


PROTOPLASM  5 

(Fig.  5).  Prolongations  from  the  surrounding  capsule-cells  have  been 
described  as  entering  these  canals  and  as  performing,  together  with  the 
lymph,  a  nutritive  function.  Hence  the  network  of  canals  has  been  called 
trophospongium.  But  it  has  not  been  shown  conclusively  that  these 
canals  open  to  the  exterior  of  the  cell.  They  may  be  similar  to  the  closed 
networks  or  "reticular  apparatus"  lying  wholly  within  the  protoplasm, 
shown  in  Fig.  6.  Such  networks  have  been  described  in  nerve  cells,  carti- 
lage cells  and  gland  cells.  The  network  is  said  to  be  of  a  thick  fluid  con- 
sistency. In  certain  gland  cells  there  are  canals  within  the  protoplasm, 
which  convey  the  secretion  to  the  free  surface  of  the  cell.  These  may  be 
simple,  branched,  or  arranged  in  a  network.  Like  the  other  forms  of 
intracellular  canals,  they  can  be  studied  only  in  special  preparations. 

5.  Inclusions.  Various  foreign  bodies,  such  as  other  cells  or  bacteria, 
which  may  have  been  ingested  by  the  protoplasm,  are  grouped  as  inclu- 
sions. This  term  is  applied  also  to  crystalloid  substances  formed  within 
the  protoplasm  (Fig.  7),  and  to  coarse  masses  of  pigment  granules  which 
appear  extraneous. 

NUCLEUS. 

The  nucleus  (Latin,  nucleus,  "the  kernel  of  a  nut";  Greek,  /capvov,  "a 
nut")  is  typically  a  well-defined  round  body,  situated  near  the  center  of 
the  cell,  appearing  denser  or  more  coarsely  granular  than  the  surrounding 
protoplasm  (Fig.  i).  There  are  characteristic  variations  in  the  shapes  of 
nuclei,  in  their  position  within  the  cells  and  in  their  structure. 

Ordinarily  the  karyoplasm,  or  nuclear  substance,  is  sharply  marked  off 
from  the  cytoplasm  by  the  nuclear  membrane.  Sometimes,  in  preserved 
tissues,  the  cytoplasm  has  shrunken  away  from  the  nuclear  membrane, 
so  as  to  leave  a  narrow  space  partially  encircling  it;  and  in  certain  living 
cells,  the  nucleus  migrates  through  cytoplasm,  as  if  it  were  an  independent 
body.  But  there  are  phases  of  cell-development  ;n  which  the  nuclear 
membrane  disappears  and  no  line  can  be  drawn  between  karyoplasm  and 
cytoplasm.  At  all  times  they  have  a  common  structural  basis.  The 
ground  substance  of  the  nucleus,  corresponding  with  the  hyaloplasm,  is 
the  nuclear  sap;  and  it  contains,  for  spongioplasm,  a  meshwork  of  delicate 
linin  fibrils.  These  help  to  form  the  nuclear  membrane,  in  which  they 
terminate.  The  nuclear  membrane,  nuclear  sap,  and  linin  reticulum  do 
not  stain  deeply,  and  are  therefore  grouped  together  as  the  achromatic 
constituents  of  the  nucleus. 

The  principal  chromatic  constituent  of  the  nucleus  is  known  as  chroma- 
tin.  It  stains  deeply,  since  it  contains  a  large  amount  of  nucleic  acid, 
which  has  a  marked  affinity  for  basic  stains.  Chromatin  occurs  in  the 
form  of  granules,  which  are  bound  together  in  strands  or  masses  by  the 


6  HISTOLOGY 

linin  fibers  (Fig.  i).  The  masses,  known  as  chromatin  knots,  occur  espe- 
cially at  the  points  of  intersection  in  the  linin  meshwork.  Sometimes  they 
are  attached  to  the  nuclear  membrane,  or  so  distributed  over  its  surface 
that  it  appears  to  consist  of  chromatin.  It  forms  morphologically  the 
most  important  part  of  the  nucleus. 

Certain  nuclei  contain  one  or  more  round  bodies,  which  belong  with 
the  chromatic  elements  because  of  their  deep  staining,  but  which  are 
chemically  different  from  chromatin.  These  bodies,  known  as  nucleoli, 
are  stained  with  acid  or  neutral  dyes.  They  are  said  to  be  composed  of 
paranuclein,  whereas  chromatin  is  composed  of  nuclein.  In  distilled 
water  the  structures  formed  of  nuclein  disappear,  but  those  consisting  of 
paranuclein  remain.  The  nuclei  of  nerve  cells  contain  typical  nucleoli 
(Figs.  3  and  5).  Sometimes  a  nucleolus,  lodged  in  the  nuclear  reticulum, 
is  more  or  less  covered  with  chromatin  (Fig.  9,  A),  but  the  term  should 
not  be  applied  to  irregular  knots  of  chromatin,  even  when  most  of  the 
chromatic  material  within  a  nucleus  is  gathered  into  one  or  two  such 
bodies.  These  are  the  so-called  false  nucleoli  (pseudonucleoli) . 

Every  nucleus,  therefore,  consists  of  ground  substance  or  nuclear  sap, 
a  network  of  linin,  and  granules  and  masses  of  chromatin.  Usually  it  is 
surrounded  by  a  membrane,  and  sometimes  it  contains  a  nucleolus.  Most 
cells  contain  a  single  nucleus;  but  occasionally  a  single  cell  contains  two 
nuclei,  as  is  frequent  in  the  liver,  or  even  several  nuclei,  as  in  certain  cells 
associated  with  bone.  Non-nucleated  bodies,  like  the  mammalian  red 
blood  corpuscles,  and  the  dead  outer  cells  of  the  skin,  have  lost  their 
nuclei  in  the  course  of  development.  ,  • 

Functionally  the  nucleus  is  regarded  as  a  center  for  chemical  activities 
necessary  for  the  life  of  the  cell.  It  is  believed  to  produce  substances 
which  pass  out  into  the  cytoplasm,  where  they  maybe  further  elaborated. 
Evidences  of  nuclear  extrusions  into  the  cytoplasm  have  been  frequently 
recorded.  But  the  interactions  between  nucleus  and  cytoplasm,  of  such 
nature  that  they  cannot  be  observed  under  the  microscope,  are  presum- 
ably of  far  greater  biological  importance. 

CENTROSOME. 

-  The  centrosome  is  typically  a  minute  granule  in  the  center  of  a  small 
sphere  of  differentiated  protoplasm.  Often  the  term  is  applied  to  this 
entire  structure,  but  it  refers  particularly  to  the  central  granule;  the 
enveloping  sphere  is  known  as  the  attraction  sphere,  and  it  is  composed 
of  archoplasm.  When  a  cell  is  about  to  divide,  delicate  fibrils,  either  re- 
arranged from  the  protoplasmic  reticulum  or  formed  anew,  radiate  from 
the  archoplasm  toward  the  periphery  of  the  cell.  The  central  granule 
becomes  subdivided  into  two,  which  then  move  apart.  In  resting  cells, 


CENTROSOME  7 

or  those  which  are  not  undergoing  division,  the  centrosome  may  already 
have  divided  into  a  double  body  or  diplosome  preparatory  to  the  next 
division  of  the  cell  (Fig.  i). 

Centrosomes  have  been  detected  in  many  forms  of  resting  cells,  and 
it  is  assumed  by  some  authorities  that  the  centrosome  is  an  invariable 
constituent  of  the  cells  of  the  higher  vertebrates.  According  to  this 
opinion  the  centrosome  may  become  inconspicuous  but  it  never  loses 
its  identity.  Often  they  are  found  very  close  to  the  nuclear  membrane, 
which  may  be  indented  to  accommodate  them;  and  rarely,  as  in  certain 
cancer  cells  and  in  one  form  of  the  worm  Ascaris,  they  have  been  reported 
as  within  the  nucleus.  They  may  occur  near 
the  free  surface  of  certain  cells,  usually  in  the 
form  of  diplosomes,  as  shown  in  cell  a,  Fig.  8. 
Just  above  the  diplosome,  such  cells  may  send 
out  contractile  projections  of  protoplasm 
(pseudopodia) ,  with  the  activity  of  which  the 
diplosome  may  be  in  some  way  associated. 
Pseudopodia,  with  an  underlying  diplosome, 
have  been  observed  in  the  columnar  cells  of 
the  human  large  intestine.  In  cell  b  of  Fig.  8 
there  are  four  diplosomes,  one  of  which  lies 
beneath  the  protoplasmic  projections.  It  is 
believed  that  the  diplosomes  may  multiply 

by  fission,  and  that  thus  they  may  give  rise  to  the  numerous  motile 
hairs,  or  cilia,  which  project  from  certain  cells.  Of  th^se  they  form  the 
basal  bodies  (Fig.  8,  c).  In  many  gland  cells  the  centrosome  lies  in  the 
midst  of  the  protoplasm  where  the  secretion  accumulates.  The  discharge 
of  the  secretion  is  accomplished  by  the  contraction  of  the  protoplasmic 
strands  in  which  the  centrosome  is  lodged.  In  all  these  relations  the 
centrosome  appears  to  be  a  center  for  motor  activities,  and  it  is  described 
as  the  kinetic  or  dynamic  center  of  the  cell. 


FIG.  8. — CELLS  OF  THE  EFFERENT 
DUCTS  OF  THE  TESTIS  OF  A 
MOUSE.  (After  Puchs.) 

To  show  diplosomes,  and  (in  c) 
cilia  with  basal  bodies. 


CELL  WALL. 

The  protoplasm  at  the  surface  of  certain  cells  floating  in  the  blood  or 
lymph  forms  a  thin  pellicle,  apparently  as  a  result  of  protoplasmic  con- 
centration, or  other  reaction  to  the  surrounding  medium.  Cells  which 
line  the  greater  part  of  the  digestive  tube,  and  have  only  one  surface 
directed  toward  the  intestinal  contents,  are  provided  with  a  thick  wall  on 
the  exposed  surface.  Such  a  wall  is  called  a  cuticular  border,  or  cuticvla. 
On  the  other  sides  of  these  cells,  the  membrane  is  much  thinner,  and  on 
the  basal  surface  it  is  sometimes  lacking.  In  such  cases  the  protoplasm 
appears  to  be  continuous  with  that  of  the  underlying  cells.  In  other  cases 


8  HISTOLOGY 

the  entire  cell  is  devoid  of  any  membrane.  The  cell  membrane,  therefore, 
is  not  an  essential  part  of  a  cell;  if  present  it  ranges  from  a  thin  pellicle, 
on  the  border  line  of  visibility,  to  a  well-defined  wall,  which  may  be  formed 
as  a  secretion  of  the  underlying  protoplasm.  If  the  several  surfaces 
of  the  cell  are  in  relation  to  different  environments,  there  is  often  a  corre- 
sponding difference  in  the  structure  of  their  walls. 

In  examining  a  group  of  cells,  it  will  be  important  to  determine  whether 
they  are  merely  in  contact,  or  actually  continuous.  Sometimes  cells 
are  so  completely  fused  that  their  nuclei  are  irregularly  distributed  through 
a  single  mass  of  protoplasm.  Such  a  formation  is  a  syncytium  in  which 
the  position  of  the  nuclei  is  the  only  means  of  estimating  the  territory  of  a 
single  cell.  A  syncytium  may  arise  from  the  fusion  of  cells,  or,  as  in  stri- 
ated muscle  fibers,  it  may  be  due  to  the  multiplication  of  nuclei  in  an  un- 
divided mass  of  protoplasm.  Instead  of  being  completely  fused,  cells  are 
often  joined  to  one  another  by  protoplasmic  processes  of  varying  length 
and  width,  thus  forming  cellular  networks.  Fibrils  within  such  a  syncy- 
tium may  pass  continuously  from  the  protoplasm  of  one  cell  into  that  of 
another. 

Although  cell  membranes  are  often  inconspicuous  in  animal  cells,  they  cannot  be 
overlooked  in  plants.  Thus  cork  is  a  mass  of  dead  cells  from  which  nuclei  and  proto- 
plasm have  disappeared,  leaving  only  the  cell  walls.  In  describing  cork,  Robert 
Hooke  introduced  the  name  "cell,"  in  1664.  He  wrote:  "I  took  a  good  clear  piece  of 
Cork  and  with  a  Pen-knife  sharpen'd  as  keen  as  a  Razor,  I  cut  a  piece  of  it  off,  and 
thereby  left  the  surface  of  it  exceeding  smooth,  then  examining  it  very  diligently  with 
a  Microscope,  me  thought  I  could  perceive  it  to  appear  a  little  porous.  .  .  .  These 

pores,  or  cells,  were  not  very  deep,  but  consisted  of  a  great  many  little  Boxes ." 

In  this  way  one  of  the  briefest  and  most  important  of  scientific  terms  was  introduced. 


FORM  AND  SIZE  OF  CELLS. 

Cells  are  regarded  as  primarily  spherical  in  form.  Spherical  cells 
are  comparatively  numerous  in  the  embryo,  and  in  the  adult  the  resting 
white  blood  corpuscles,  which  float  freely  in  the  body  fluids,  assume  this 
shape.  Such  cells  are  circular  in  cross  section.  When  spherical  cells 
are  subjected  to  the  pressure  of  similar  neighboring  cells,  they  become 
polyhedral  and  usually  appear  six-sided  in  cross  section.  Such  cells,  as 
a  whole,  may  be  cuboidal,  columnar,  or  flat.  Certain  cells  become  fusi- 
form (spindle-shaped)  or  are  further  elongated  so  as  to  form  fibers;  others 
send  out  radiating  processes  and  are  called  steHate.  Thus  the  form  of 
cells  is  extremely  varied.  The  shape  of  the  nucleus  tends  to  correspond 
with  that  of  its  cell.  It  is  usually  an  elliptical  body  in  elongated  cells, 
and  spherical  in  round  or  cuboidal  cells.  In  stellate  cells  it  is  either 
spherical  or  somewhat  elongated.  Crescentic  nuclei,  and  others  more 


SIZE   OF   CELLS  9 

deeply  and  irregularly  lobed,  are  found  in  some  of  the  white  blood  cor- 
puscles and  in  giant  cells. 

The  size  of  cells  ranges  from  that  of  the  yolks  of  birds'  eggs — which  are 
single  cells,  at  least  shortly  before  being  laid — down  to  microscopic  struc- 
tures four  thousandths  of  a  millimeter  in  diameter.  The  thousandth  of  a 
millimeter  is  the  unit  employed  in  microscopic  measurements.  It  is  called 
a  micron,  and  its  symbol  is  the  Greek  letter  ju.  The  small  cells  referred  to 
are  therefore  four  microns  (4  ju)  in  diameter.  The  size  of  any  structure 
in  a  section  of  human  tissue  may  be  roughly  estimated  by  comparing  its 
dimensions  with  the  diameter  of  a  red  blood  corpuscle  found  in  the  same 
section.  These  red  corpuscles  are  quite  uniformly  7.5  ^  in  diameter. 

CYTOMORPHOSIS. 

Cytomorphosis  is  a  comprehensive  term  for  the  structural  modifica- 
tions which  cells,  or  successive  generations  of  cells,  undergo  from  their 
origin  to  their  final  dissolution.1  In  the  course  of  their  transformation, 
cells  divide  repeatedly,  but  the  new  cells  begin  development  where  the 
parent  cells  left  off.  Cell  division,  therefore,  is  an  unimportant  incident 
in  cytomorphosis. 

Cytomorphosis  is  a  continuous  advance  in  which  four  successive  stages 
are  recognized — first,  the  stage  in  which  the  cells  are  undifferentiated; 
second,  the  stage  of  specialization  or  differentiation;  third,  the  stage  of 
degeneration;  and  fourth,  the  stage  in  which  the  cells  die  and  are  removed. 
These  may  be  considered  in  turn. 

Undifferentiated  cells,  as  can  be  seen  in  sections  of  young  embryos, 
are  characterized  by  large  nuclei  and  little  protoplasm.  They  multiply 
rapidly,  but  the  rate  of  division  declines  with  the  gradual  increase  of  the 
protoplasm  and  the  consequent  functional  differentiation  of  the  cell.  In 
the  adult,  relatively  undifferentiated  cells  are  found  in  many  situations, 
as,  for  example,  in  the  deepest  layer  of  the  epidermis.  As  the  cells  at  the 
surface  die  and  are  cast  off,  new  ones  come  up  from  below  to  take  their 
places.  But  since  the  basal  cells  can  produce  only  epidermal  cells,  they 
are  themselves  partly  differentiated.  From  this  point  of  view  the  fertil- 
ized ovum,  which  can  produce  all  kinds  of  cells,  must  be  regarded,  in  spite 
of  its  size  and  great  mass  of  yolk-laden  protoplasm,  as  the  least  differenti- 
ated cell. 

Differentiated  cells  may  preserve  a  round  or  cuboidal  form,  but  usually 
they  are  elongated,  flattened,  or  stellate.  The  cytoplasm  usually  con- 
tains coarse  granules,  fibrils,  masses  of  secretion  or  other  special  forma- 

1  The  term  cytomorphosis  was  introduced  by  C.  S.  Minot  in  1901  in  a  lecture  entitled  "The 
Embryological  Basis  of  Pathology"  (Science,  1901,  vol.  13,  p.  494).  Cytomorphosis  is  further 
discussed  by  Professor  Minot  in  "The  Problem  of  Age,  Growth,  and  Death,"  published  by  G.  P. 
Putnam's  Sons,  1908. 


IO 


HISTOLOGY 


tions.  As  a  result  of  their  own  protoplasmic  activity,  the  cells  of  many 
tissues  become  surrounded  by  inter cellidar  substances,  which  may  far 
exceed  in  bulk  the  cells  which  produced  them.  Intercellular  substances 
may  be  solid  or  fluid.  When  present  in  small  amount  they  form  thin 
layers  of  cement  substance  between  closely  adjacent  cells;  in  large  amount 
these  substances  constitute  a  ground  work  in  which  the  cells  are  imbedded, 
as,  for  example,  in  cartilage  and  bone. 

Although  the  differentiation  of  cells  is  chiefly  cytoplasmic,  there  is 
some  evidence  of  corresponding  nuclear  changes.  Thus  while  the  muscle 

cells  of  the  salamander  are  elabor- 
ating complex  fibrils,  the  nuclei 
become  modified  as  shown  in  Fig. 
9.  The  significance  of  the  nuclear 
changes  is  unknown. 

Degeneration  is  the  manifesta- 
tion of  the  approaching  death  of 
the  cell.  In  nerve  cells  this  process 
normally  takes  place  very  slowly. 
These  cells  remain  active  through- 
out life,  and  if  destroyed,  they 
can  never  be  replaced.  In  many 
glands,  in  the  blood  and  in  the 
skin,  however,  the  cells  are  con- 
stantly dying  and  new  ones  are 
being  differentiated.  In  a  few 
organs  the  cells  perish,  but  no  new 
ones  form,  so  that  the  organ  to 
which  they  belong  atrophies. 
Thus  a  large  part  of  the  meso- 
nephros  (Wolffian  body)  disap- 
pears during  embryonic  life;  the 
thymus  becomes  vestigial  in  the 

adult;  and  the  ovary  in  later  years  loses  its  chief  function  through  the 
degeneration  of  its  cells. 

The  optical  effects  of  degeneration  cannot  at  present  be  properly  classi- 
fied. In  a  characteristic  form,  known  as  " cloudy  swelling,"  the  cell  en- 
larges, becoming  pale  and  opaque.  In  another  form  the  cell  shrinks  and 
stains  deeply,  becoming  either  irregularly  granular  or  homogeneous  and 
hyaline.  The  nucleus  may  disappear  as  if  in  solution  (karyolysis,  chroma- 
tolysis) ;  or  it  may  become  densely  shrunken  or  pycnotic,  and  finally  break 
into  fragments  and  be  scattered  through  the  protoplasm  (karyorhexis) . 
If  the  process  of  degeneration  is  slow,  the  cell  may  divide  by  amitosis. 
It  may  be  able  to  receive  nutriment  which  it  cannot  assimilate,  and  thus 


FIG.  9. — 'NUCLEI  OF  STRIATED  MUSCLE  FIBERS  FROM 
YOUNG  . SALAMANDERS  (NECTURUS).  (Eycleshy- 
mer.) 

A,  From  a  7  mm.  embryo;  B,  from  one  of  26  mm.;  ch, 
chromatin  knot;  g.  s,  ground  substance;  1,  linin 
fibril;  n,  nucleolus;  n.m,  nuclear  membrane. 


CYTOMORPHOSIS  1 1 

its  protoplasm  may  be  infiltrated  with  fat  and  appear  vacuolated.  It 
may  form  abnormal  intercellular  substances,  for  example,  amyloid;  or 
the  existing  intercellular  substances  may  become  changed  to  mucoid 
masses,  or  have  lime  salts  deposited  in  them.  Thus  an  impairment  or 
perversion  of  function  is  often  associated  with  optical  changes  in  the  cell 
substance. 

The  removal  of  dead  cells  is  accomplished  in  several  ways.  Those 
near  the  external  or  internal  surfaces  of  the  body  are  usually  shed  or  des- 
quamated, and  such  cells  may  be  found  in  the  saliva  and  urine.  Those 
which  are  within  the  body  may  be  dissolved  by  chemical  action  or  de- 
voured by  phagocytes. 

Every  specimen  of  human  tissue  exhibits  some  phase  of  cytomorphosis. 
In  some  sections  a  series  of  cells  may  be  observed  from  those  but  slightly 
differentiated,  to  those  which  are  dead  and  in  process  of  removal.  Because 
of  the  similarity  and  possible  identity  of  this  normal  "physiological" 
regression,  with  that  found  in  diseased  tissues,  such  specimens  should  be 
studied  with  particular  care. 

VITAL  PHENOMENA. 

The  vital  properties  of  cells  are  fully  treated  in  text-books  of  physi- 
ology. They  include  the  phenomena  of  irritability,  metabolism,  con- 
tractility, conductivity,  and  reproduction.  Under  irritability  may  be 
grouped  the  response  of  cells  to  stimuli  of  various  sorts,  such  as  heat,  light, 
electricity,  chemical  reagents,  the 
nervous  impulse,  or  mechanical  inter- 
ference. Metabolism,  in  a  wide  sense, 
includes  the  ingestion  and  assimila 
tion  of  food,  the  elaboration  and 
secretion  of  desirable  products,  to- 
gether with  the  elimination  of  waste 
products.  Contractility  may  be 
manifest  in  the  locomotion  of  the  %&w^$£t^^  th~e  observation: 
entire  cell,  in  the  vibratile  action  of 

slender  hair-like  processes,  the  -cilia,  or  in  contraction  of  the  cell  body. 
Conductivity  is  the  power  of  conveying  impulses  from  one  part  of  the 
cell  to  another.  Reproduction  is  seen  in  the  process  of  cell  division. 
Many  phases  of  these  activities  are  observed  in  microscopic  sections  and 
as  such  they  will  be  referred  to  in  later  chapters.  A  few  which  are  of 
general  occurrence  will  be  described  presently. 

AMCEBOID  MOTION. 

The  unicellular  animal,  Amoeba,  exhibits  a  type  of  motility  known 
as  amoeboid,  which  has  been  observed  in  many  sorts  of  cells  in  the  verte- 


12  HISTOLOGY 

brate  body.  In  marked  cases,  as  in  certain  white  blood  corpuscles  (the 
leucocytes),  the  cell  protoplasm  sends  out  fine  or  coarse  processes  which 
divide  or  fuse  with  one  another,  causing  the  cell  to  assume  a  great  variety 
of  forms.  The  processes  may  be  retracted,  or  they  may  become  attached 
somewhere  and  draw  the  remainder  of  the  cell  body  after  them,  the  result 
of  which  is  locomotion  or  the  so-called  wandering  of  the  cell.  Such  wander- 
ing cells  play  an  important  part  in  the  economy  of  the  animal  body. 
Their  processes  can  flow  around  granules  or  cells  and  thus  enclose  them 
in  protoplasm.  Some  of  these  ingested  bodies  may  be  assimilated  by 
the  cell  as  a  result  of  complex  chemical  and  osmotic  reactions.  Cells 
which  feed  on  foreign  particles  and  can  alter  or  digest  them  are  known  as 
phagocytes.  Amoeboid  movements  take  place  very  slowly.  In  prepara- 
tions from  warm-blooded  animals  they  may  be  accelerated  by  gently 
heating  the  object. 

Another  form  of  motion  is  that  which  occurs  within  the  protoplasm 
of  fresh  cells,  whether  living  or  dead,  and  consists  in  a  rapid  oscillation 
of  minute  granules,  due  to  diffusion  currents.  Although  these  movements 
were  first  observed  within  protoplasm,  it  was  soon  shown  that  they  oc- 
curred when  various  inert  particles  were  suspended  in  a  liquid.  Robert 
Brown  described  the  motion  in  1828,  in  an  essay  entitled  "On  the  General 
Existence  of  Active  Molecules  in  Organic  and  Inorganic  Bodies,"  and 
the  phenomenon  is  called  the  molecular  or  Brownian  movement.  It 
may  often  be  seen  in  salivary  corpuscles. 


FORMATION  AND  REPRODUCTION  OF  CELLS. 

In  the  past,  two  sorts  of  cell  formation  have  been  recognized,  namely 
the  spontaneous  generation  of  cells,  and  the  origin  of  cells  through  the 
division  of  pre-existing  cells.  According  to  the  theory  of  spontaneous 
generation  it  was  once  thought  that  animals  as  highly  organized  as  intes- 
tinal worms  came  into  existence  from  the  fermentation  of  the  intestinal 
contents.  After  this  had  been  disproved,  it  was  still  thought  that  uni- 
cellular animals  arose  spontaneously  and  that  cells  might  be  formed 
directly  from  a  suitable  fluid,  the  cytoblastema.  Something  of  the  sort 
may  have  occurred  when  life  began,  and  it  is  the  expectation  of  certain 
investigators  that  conditions  may  yet  be  produced  which  shall  lead  to 
the  formation  of  organic  bodies  capable  of  growth  and  reproduction.  At 
present,  however,  only  one  source  of  cells  is  recognized — the  division  of 
existing  cells.  "Omnis  cellula  e  cellula."  A  nucleus  likewise  can  arise 
only  by  the  division  of  an  existing  nucleus;  it  cannot  be  formed  from  non- 
nucleated  protoplasm. 


DIRECT  DIVISION  13 

AMITOSIS. 

The  simplest  form  of  cell  division  is  one  which  rarely  occurs.  Ordina- 
rily the  division  of  the  cell  is  accompanied  with  the  production  of  proto- 
plasmic filaments,  and  the  process  is  therefore  called  mitosis  (Greek,  /UTOS, 
a  thread) .  B  lit  in  direct  division '  or  amitosis  these  filaments  are  not 
developed.  The  nucleus  merely  becomes  increasingly  constricted  at 
the  middle  until  divided  in  two;  or  it  may  be  bisected  by  a  deep  cleft  or 
fissure.  Preceding  the  division  of  the  nucleus,  the  nucleolus,  if  present, 
may  subdivide  and  supply  each  half  of  the  nucleus  with  a  nucleolus  (Fig. 
n).  Cells  which  divide  by  this  method  are  usually  degenerating,  and 


Beginning  Completed  Beginning  Completed 


Division  of  the  nucleolus.  Division  of  the  nucleus. 

FIG.  11. — AMITOSIS  IN  EPITHELIAL  CELLS  FROM  THE  BLADDER  OF  A  MOUSE.     Xs6o. 
Such  preparations   as  that  shown  in  the  figure  are  made  by  pressing  the  lining  of  a  freshly  obtained 
piece  of  the  bladder  against  a  clean  cover-glass.     Certain  of  the  superficial  cells  adhere  to  it,  and  they  are 
then  fixed  and  stained. 

the  process  may  terminate  with  the  multiplication  of  nuclei.  If  carried 
to  completion,  the  protoplasm  also  divides,  and  a  cell  membrane  develops 
between  the  daughter  nuclei.  The  role  of  the  centrosome  in  amitosis 
has  not  been  determined.  Maximow  finds  it  in  a  passive  condition 
between  the  two  halves  of  the  nucleus,  or  beside  the  stalk  connecting 
these  halves  if  the  division  is  not  complete  (Anat.  Anz.,  1908,  vol.  33,  p. 
89).  He  states  that  certain  mesenchymal  cells  which  divide  by  amitosis 
in  the  rabbit  embryo  are  not  degenerating,  but  may  later  divide  by  mito- 
sis, and  thus  he  confirms  Patterson's  similar  conclusion  in  regard  to  cer- 
tain cells  in  the  pigeon's  egg.  These  instances  are  regarded  as  exceptional. 
In  the  human  body  the  detachment  of  a  portion  of  the  lobate  nucleus 
of  certain  leucocytes  has  been  described  as  amitotic  division,  but  the 
superficial  cells  of  the  bladder  furnish  more  typical  examples.  E.  F. 
Clark  has  found  many  cells  dividing  by  amitosis  in  the  degenerating  parts 
of  a  human  cancer.  The  occurrence  of  two  nuclei  within  one  cell  by  no 
means  indicates  this  form  of  division.  Associated  with  such  cells,  others 
containing  nuclei  of  the  dumb-bell  shape,  or  those  partially  bisected 
by  clefts  must  be  found,  in  order  to  prove  that  amitotic  division  is  taking 
place. 


14  HISTOLOGY 

MITOSIS. 

Mitosis,  also  called  indirect  division  and  karyokinesis,  is  the  ordinary 
mode  of  cell  division.  Although  it  is  a  continuous  process,  it  has  been 
conveniently  divided  into  four  successive  phases — the  prophase,  metaphase, 
anaphase,  and  telophase.  During  the  prophase  the  chromatic  material 
of  the  nucleus  prepares  for  division  and  collects  in  the  center  of  the  cell. 
It  is  divided  in  halves  in  the  metaphase,  and  the  two  halves  move  apart 
during  the  anaphase.  The  chromatic  material  becomes  reconstructed 
into  resting  nuclei  during  the  telophase.  The  various  patterns  which  the 
chromatic  material  and  protoplasmic  fibrils  present  during  these  phases 
are  known  as  mitotic  figures. 

Mi  to  tic  figures  are  found  in  all  rapidly  growing  tissues,  but  especially 
favorable  for  preliminary  study  are  the  large  cells  in  the  root  tips  of  plants. 
In  longitudinal  sections  of  root  tips,  the  cells  are  cut  at  right  angles  to 
the  plane  of  cell  division,  which  is  desirable;  and  often  in  a  single  section 
5  mm.  long,  all  the  fundamental  stages  may  be  quickly  located.  The 
following  general  description  of  mitosis  is  based  upon  such  easily  ob- 
tained preparations,  and  the  plant  selected  is  the  spiderwort  (Trade- 
scantia  virginiana)  .l  They  may  be  satisfactorily  stained  with  saffranin, 
or  with  iron  haematoxylin  and  a  counter  stain  such  as  orange  G.  There 
are  many  descriptions  of  mitosis  in  root  tips,  among  them  the  following: 

Rosen,  (Hyacinthus  orienlalis)  Beitr.  zur  Biol.  der  Pflanzen,  1895, 
vol.  7, pp.  225-312;  Nemec,  (Allium  cepa)  Sitz.-ber.  kon.  Ges.  der  Wiss. 
Prag,  1897,  No.  33,  pp.  25-26,  and  Jahrb.  fur  wiss.  Bot,  1899,  vol.  33,  pp. 
313-336;  Schaffner,  (Allium  cepa)  Bot.  Gaz.,  1898,  vol.  26,  pp.  225-238; 
Hof,  (Ephedra  major)  Bot.  Centralbl.,  1898,  vol.  76,  pp.  63-69,  113-118, 
166-171,  221-226;  Gregoire  and  Wygaerts,  (Trillium  grandifiorum)  La 
Cellule,  1904,  vol.  21,  pp.  1-76;  Farmer  and  Shove,  (Tradescentia  virgin- 
iana) Quart.  Journ.  Micr.  Sci.,  1905,  vol.  48,  pp.  559-569;  Richards, 
(Podophyllum  peltatum)  Kansas  Univ.  Sci.  Bull.,  1909,  vol.  5,  p.  87-93. 

The  cells  to  be  described  are  found  in  the  interior  of  the  root  tip,  just 
back  of  the  protecting  cap  of  cells  which  covers  its  extremity.  They  are 
oblong  in  shape  and  their  long  axis  corresponds  with  that  of  the  root. 
The  walls  are  very  distinct,  and  the  cells  consist  of  granular  vacuolated 
protoplasm,  which  in  preserved  specimens  is  generally  irregularly  shrunken. 

The  resting  cells  (Fig.  12,  A)  contain  large  round  nuclei  in  which  the 
chromatin  is  in  the  form  of  fine  granules  evenly  distributed  throughout 
the  nucleus.  A  nucleus  usually  contains  from  two  to  five  round  nucleoli, 
each  of  which,  when  in  focus,  is  seen  to  be  surrounded  by  a  clear  zone. 
The  nuclear  membrane  is  distinct. 

1  Good  specimens  may  be  obtained  from  any  rapidly  growing  root  tip.  Those  starting  from 
hyacinth  bulbs  placed  in  water  are  very  favorable.  Onion  root  tips  have  been  extensively 
used,  and  also  those  of  bean  and  corn  seedlings.  The  pointed  ends  are  snipped  off  and  dropped 
into  Flemming's  stronger  solution. 


INDIRECT  DIVISION  15 

Prophase.  The  first  indication  of  approaching  division  is  a  change 
in  the  chromatin,  which  becomes  gathered  into  fewer  and  coarser  granules 
and  takes  a  deeper  stain.  Portions  of  the  linin  network  break  down,  so 
that  the  chromatin  granules  come  to  be  arranged  in  long  convoluted 
threads.  Such  threads  are  developing  in  the  cell,  Fig.  12,  B,  but  are 
more  perfectly  formed  in  C.  It  is  possible  that  at  a  certain  stage  the 
nucleus  contains  only  a  single  continuous  thread,  but  this  condition  can- 
not be  demonstrated  in  Tradescantia.  The  stage  of  nuclear  division  in 
which  the  chromatic  material  appears  to  be  arranged  in  a  coiled  thread 
or  skein  is  called  a  spireme.  The  "close  spireme"  (B)  is  succeeded  by 
the  " loose  spireme"  (C).  Successive  stages  in  the  development  of  the 
spireme  in  animal  cells  are  seen  in  Fig.  20,  D,  E,  and  F. 

As  the  spireme  develops,  the  nuclear  membrane  becomes  less  distinct, 
and  the  clear  zones  disappear  from  around  the  nucleoli.  The  nucleoli 
become  apparently  less  regular  in  outline,  and  forms  which  suggest  that 
two  of  them  have  fused  (Fig.  12,  B)  are  perhaps  more  frequently  seen 
than  in  resting  cells.  Usually  it  is  stated  that  the  nucleoli  break  up  into 
smaller  bodies  toward  the  time  of  their  dissolution,  and  that  some  of 
these  escape  into  the  cytoplasm  after  the  disappearance  of  the  nuclear 
membrane.  Farmer  and  Shove  believe  that  the  nucleoli  contribute  to 
the  chromatin ;  Richards  regards  them  as  a  store  of  food  material  for  the 
rest  of  the  cell;  and  others  believe  that  they  form  the  achromatic 
" spindle''  which  will  be  described  presently.  Their  function  in  animal 
cells  is  equally  uncertain. 

In  the  stage  shown  in  Fig.  12,  D,  which  may  be  regarded  as  the  end 
of  the  prophase,  the  nuclear  membrane  and  the  nucleoli  have  disappeared, 
and  the  spireme  thread  has  become  divided  into  a  number  of  segments 
or  chromosomes.  These  are  straight  or  curved  rods  of  different  lengths. 
Sometimes  they  appear  as  bent  V-shaped  bodies,  but  these  often  represent 
two  chromosomes  with  their  ends  together.  J-shaped  forms,  with  one  long 
and  one  short  arm,  have  been  described  in  various  plants.  The  chromo- 
somes become  so  arranged  that  one  end  of  the  rods,  or  the  apices  of  the  V's, 
are  situated  in  the  equatorial  plane,  which  extends  transversely  across  the 
middle  of  the  cell.  Often  it  is  temporarily  tilted  (as  in  D  and  E)  as  if  the 
mitotic  apparatus  had  shifted  to  a  position  in  which  it  obtained  more 
space.  It  may  do  this  mechanically  if  the  contents  of  the  cell  are  under 
pressure.  When  the  chromosomes  are  gathered  at  or  in  the  equatorial 
plane,  they  constitute  collectively  the  equatorial  plate.  Because  of  their 
stellate  arrangement  at  this  stage,  which  is  best  seen  in  transverse  sections 
of  the  cell,  this  mitotic  figure  is  known  as  the  aster. 

The  manner  in  which  the  chromosomes  are  formed  from  the  spireme 
thread  is  difficult  to  determine.  According  to  Gregoire  and  Wygaerts, 
the  linin  and  chromatin,  which  have  often  been  regarded  as  closely  related 


i6 


HISTOLOGY 


substances,  are  identical,  and  linin  is  merely  a  name  for  slender  filaments 
of  chroma  tin.     Accordingly   the  chromatin   simply  draws   together  to 


G 

FIG.  12. — MITOTIC  CELL  DIVISION  IN  THE  ROOT  TIP  OF  Tradescantiavirginiana.      Xi2S  diam. 
A,  resting  cell;  B,  C,  D,  prophase;  E,  metaphase;  F,  anaphase;  G,  H,  I,  telophase. 

form  chromosomes,  and  the  beaded  appearance  of  the  spireme  thread  is 
due  to  alternate  enlargements  and  constrictions  of  one  substance.  Others 
consider  that  a  different  substance  connects  the  granules  of  chromatin 


,     INDIRECT   DIVISION  17 

with  one  another;  and  Rosen  states  that  each  chromatin  granule  is  com- 
pletely imbedded  in  a  broad  strand  of  linin.  Davis  similarly  interprets 
the  spireme  shown  in  Fig.  20,  F.  Whatever  the  actual  structure  may  be, 
the  chromatin  granules  in  the  spireme  thread  early  divide  in  two,  so  that 
the  thread  appears  double.  When  the  thread  shortens  and  condenses  to 
form  the  chromosomes,  the  rows  of  granules  may  coalesce  so  as  to  pro- 
duce a  rod  already  divided  lengthwise,  although  its  halves  are  in  close 
apposition.  Occasionally  the  ends  of  the  chromosomes  are  seen  to  be 
slightly  separated. 

Metaphase.  In  the  metaphase  (Fig.  12,  E),  the  two  longitudinal 
halves  of  each  chromosome  are  being  drawn  apart  toward  the  opposite 
poles  of  the  cell.  If  the  chromosome  is  V-shaped,  the  separation  of  the 
two  halves  begins  at  the  apex  of  the  V. 

At  this  stage  an  achromatic  figure,  known  as  the  spindle,  is  evident 
in  plant  cells,  but  it  is  more  sharply  defined  in  those  of  animals.  As  seen 
in  the  diagram  (Fig.  13),  it  consists  of  fibrils  which  pass  from  the  equatorial 

Polar  radiation.         Nuclear  spindle. 


jr 

_~-^ 

FIG,  13.— EARLY  METAPHASE.  FIG.  14.— LATE  METAPHASE. 

plate  toward  either  pole,  where,  in  animal  cells,  there  is  a  well-defined 
granule,  the  centrosome.  Around  each  centrosome  there  are  radiating 
protoplasmic  fibrils,  forming  the  polar  radiation  (Figs.  13  and  14).  The 
polar  radiation  is  also  called  an  aster,  and  the  two  asters  connected  by 
the  spindle  are  known  as  the  amphiaster.  Some  of  the  spindle  fibers 
are  attached  to  the  chromosomes  and  appear  to  pull  their  halves  apart; 
others  pass  from  pole  to  pole  without  connecting  with  the  chromosomes. 
In  animal  cells  the  spindle  arises  as  the  two  centrosomes,  lying  beside 
the  nucleus,  move  apart  (Fig.  20,  A).  As  they  pass  to  the  opposite  poles 
of  the  nucleus,  the  spindle  forms  between  them,  either  from  the  nuclear 
reticulum,  or  the  cytoplasmic  reticulum,  or  in  part  from  both.  These 
conditions  appear  to  vary  in  different  animals. 

In  the  cells  of  root  tips,  a  condensation  of  protoplasm  forms  a  cap  at 
the  poles  of  the  nucleus  at  the  time  when  the  nuclear  membrane  and 
nucleoli  are  disappearing.  From  the  " polar  cap,"  spindle  fibers  develop 


1 8  HISTOLOGY 

which  invade  the  nucleus,  and  also  radiations  which  have  been  traced 
even  to  the  cell  walls.  But  as  Rosen  states,  sun-like  figures,  such  as  cer- 
tain botanists  have  pictured,  do  not  occur.  Schaffner  has  described  a 
distinct  centrosome  or  central  granule  in  the  .root  tip  of  the  onion,  but 
Richards  finds  that  in  Podophyllum  there  is  no  such  structure,  and  the 
weight  of  evidence  appears  to  be  against  the  existence  of  a  definite  centro- 
some in  the  higher  plants. 

Anaphase.  In  the  anaphase  the  halves  of  each  chromosome  move  to 
the  opposite  poles  (Fig.  12,  F).  The  figure  thus  produced  is  known  as  a 
double  star  or  diaster.  Since  each  chromosome  has  divided  into  two, 
the  original  number  of  chromosomes  is  preserved,  and  an  equal  number 
of  rods  will  be  found  in  either  star.  They  cannot  all  be  brought  into 
focus  together,  and  because  of  overlapping,  they  are  hard  to  count. 
Sometimes  one  chromosome,  longer  than  the  others,  remains  for  a  time 
as  a  continuous  bar  from  one  aster  to  the  other.  Between  the  asters 
there  are  always  straight  spindle  fibers,  but  they  vary  in  distinctness. 
(The  anaphase  in  an  animal  cell  is  well  shown  in  Fig.  21,  D.) 

Telophase.  After  the  chromosomes  have  reached  the  opposite  poles,  , 
they  form  two  dense  masses.  They  are  generally  said  to  unite  end  to 
end,  thus  forming  a  spireme  thread.  But  in  the  root  tips  of  Trillium, 
Gregoire  and  Wygaerts  state  that  they  come  into  contact  with  one  another 
laterally;  and  as  they  separate,  transverse  connections  are  retained, 
which,  with  the  vacuolization  of  the  chromosomes,  restore  the  nuclear 
reticulum.  This  may  not  be  the  correct  interpretation,  but  immediately 
after  the  anaphase  the  chromosomes  form  a  very  compact  mass,  easily 
overstained  so  that  it  appears  soh'd.  Subsequently  the  mass  enlarges 
(Fig.  12,  H),  and  the  chromosomes  become  coarsely  granular,  taking  the 
form  of  wide  bands.  Nucleoli  reappear,  and  according  to  Richards, 
" it  is  a  general  rule  that  they  arise  on  the  side  of  the  nucleus  nearest  the 
new  cell  walL"  This  accords  with  Nemec's  statement  that  they  form 
from  the  outer  fibers  of  the  spindle.  Nemec  and  Rosen  agree  that  they 
first  appear  outside  of  the  nucleus,  which  they  enter  before  the  nuclear 
membrane  develops.  These  are  details  which  require  confirmation. 

The  new  cell  wall  arises  in  plants  as  a  series  of  thickenings  of  the 
interzonal  spindle  fibers,  which  at  this  stage  form  a  barrel-shaped  bundle 
(Fig.  12,  G).  The  thickenings  coalesce  to  form  a  membrane  which  does 
not  at  first  reach  the  sides  of  the  cell.  While  this  wall  is  developing  the 
nuclei  are  in  a  condition  resembling  the  spireme  stage  of  the  prophase. 
The  entire  mitotic  figure  is  therefore  called  the  double  spireme  or  di- 
spireme.  The  cell  wall  is  soon  completed  and  the  nuclei  return  to  the 
resting  condition  (Fig.  12,  I). 

The  time  required  for  mitotic  cell  division  varies  from  half  an  hour 
(in  man)  to  five  hours  (in  amphibia).  After  death,  if  the  tissues  are  not 


INDIRECT  DIVISION  1 9 

hardened  by  cold  or  reagents,  it  is  thought  that  mitoses  go  on  to  comple- 
tion. Forty-eight  hours  may  elapse  before  they  entirely  disappear  from 
the  human  body. 

Pluri-polar  mitosis.  Under  abnormal  conditions,  as  in  the  cancer 
cells  shown  in  Fig.  15,  spindles  may  develop  simultaneously  in  connection 
with  three  or  four  centrosomes.  Similar  pluri-polar  spindles  have  been 
produced  experimentally,  by  treating  cells  with  various  poisonous  solu- 
tions. An  unequal  distribution  of  chromatin  may  occur  under  such 
conditions,  and  this  may  happen  also  with  bipolar  spindles,  as  shown  in 
Fig.  15,  a. 

Number  and  individuality  of  the  chromosomes.  It  is  now  generally 
believed  that  every  species  of  plant  or  animal  has  a  fixed  and  characteris- 
tic number  of  chromosomes,  which  regularly  recurs  in  the  division  of  all 


FIG.  15. — MITOSES  IN  HUMAN  CANCER  CELLS.     (From  Wilson,  after  Galeotti.) 
Asymmetrical  mitosis  with  unequal  distribution  of  chromatin;  b,  tripolar  mitosis;  c,  quadripolar  mitosis 


its  cells,  with  the  exception  of  the  germ  cells,  in  which  the  number  is 
reduced.  In  certain  species,  however,  the  two  sexes  regularly  differ  from 
one  another  in  the  number  of  their  chromosomes,  and  one  sex  may  con- 
tain an  odd  number.  Usually  the  number  of  chromosomes  is  believed  to 
be  even. 

There  is  considerable  difficulty  in  counting  the  chromosomes.  Gener- 
ally it  is  possible  that  some  have  been  cut  away  in  the  process  of  section- 
ing, so  that,  if  the  number  is  believed  to  be  invariable,  the  highest  number 
found  in  any  cell  is  assumed  to  occur  regularly.  Another  source  of  error 
lies  in  the  fact  that  a  bent  chromosome  may  be  counted  as  two,  or  rods 
with  their  ends  overlapping  may  appear  as  one.  Farmer  and  Shove 
have  ventured  to  state  that  the  number  in  Tradescantia  "varies  from 
about  twenty-six  to  thirty- three."  Nemec  found  that  twelve  chromo- 
somes occur  regularly  in  young  tissues  of  the  onion,  but  that  in  older 
tissues  the  number  diminishes  even  to  four.  Sixteen  have  been  recorded 
in  the  onion  by  other  botanists.  Podophyllum  is  said  to  have  sixteen 
(Mottier),  but  Richards  records  counts  of  fourteen.  In  man  the  number 
has  been  placed  at  16  and  32,  but  it  is  now  believed  to  be  24.  Gutherz, 
with  particularly  favorable  material,  emphasizes  the  difficulty  of  counting 


2O  HISTOLOGY 

the  chromosomes  in  man.  He  found  only  two  cells  in  which  a  count 
could  be  made,  in  neither  case  with  absolute  certainty.  But  he  agrees 
with  Duesberg  that  the  reduced  number  is  twelve,  according  to  which 
the  whole  number  should  be  twenty-four.  Recently,  however,  Wieman 
has  found  cells  in  the  brain  of  a  g-mm.  human  embryo  which  contained  33 
chromosomes.  Some  cells  in  the  nasal  epithelium  and  mesenchyma  of 
this  specimen  contained  34,  and  others  38.  Thus  Wieman  concludes 
that  the  number  in  man  is  certainly  greater  than  24  and  is  perhaps  vari- 
able (Amer.  Journ.  Anat,  1913,  vol.  14,  pp.  416-471). 

In  the  grasshoppers,  which  are  among  the  most  favorable  objects  for 
the  study  of  mitosis,  not  only  is  the  number  of  chromosomes  for  a  given 
species  believed  to  be  constant,  but  each  cell  appears  to  contain  a  definite 
series  of  chromosomes,  the  members  of  which  vary  somewhat  in  shape 
and  size.  Recent  studies  of  such  cells  favor  Rabl's  hypothesis  of  the 
individuality  of  the  chromosomes,  according  to  which  the  chromosomes 
persist  in  the  resting  nucleus,  although  disguised  by  their  lateral  branches 
and  diffuse  granular  form.  If  this  hypothesis  is  correct,  when  a  nucleus 
prepares  for  division  the  same  chromosomes  which  entered  it  will  reappear. 
Sometimes  in  the  prophase  the  bands  of  chromatin  are  arranged  in  a 
polar  field  such  as  is  seen  in  the  telophase  (Fig.  12,  H).  This  arrange- 
ment has  been  observed  by  Farmer  and  Shove  in  the  prophase  of  Trades- 
cantia,  and  by  others  in  various  plants  and  animals.  It  is  regarded  as 
evidence  that  the  chromosomes  are  "independent  and  continuously 
perpetuated  organs  of  the  cell."  Nevertheless  it  is  generally  true  that 
in  resting  nuclei  no  trace  of  individual  chromosomes  can  be  made  out. 
The  great  importance  of  accurate  knowledge  of  the  chromosomes  is  shown 
by  the  following  considerations. 

As  a  result  of  mitotic  cell  division,  it  is  evident  that  every  new  cell 
regularly  receives  one-half  of  each  chromosome  found  in  the  parent  cell,  and 
thus  the  number  of  chromosomes  remains  constant.  But  in  the  germ 
cells  the  number  is  invariably  reduced,  and  in  some  animals  it  becomes 
exactly  one-half  of  the  number  found  elsewhere  in  the  body.  In  such  a 
case,  when  the  male  sexual  cell,  or  spermatozoon,  unites  with  the  female 
sexual  cell,  or  mature  ovum,  in  the  process  of  fertilization,  the  original 
number  is  restored.  Each  parent  thus  contributes  one-half  of  the  chromo- 
somes found  in  the  cell  which  gives  rise  to  a  new  individual;  and  since 
each  of  these  divides  with  every  subsequent  cell  division,  it  is  evident 
that  one-half  of  the  chromatin  in  every  cell  of  the  adult  body  is  of  mater- 
nal origin  and  one-half  of  paternal  origin.  The  process  by  which  the 
sexual  cells  acquire  the  reduced  number  of  chromosomes  and  become 
ready  for  fertilization  is  known  as  maturation.  The  production  of  the 
sexual  cells  in  the  male  is  called  spermatogenesis  and  in  the  female 
oo  genesis. 


SPERMATOGENESIS 


21 


SPERMATOGENESIS. 

In  its  essential  features,  the  process  of  spermatogenesis  in  insects 
corresponds  with  that  in  mammals,  and  very  favorable  material  can^be 
obtained  in  abundance  from  grasshoppers  of  various 
genera. 

The  males  may  be  distinguished  from  the  females  by  the 

shape  of  the  abdomen.     In  males  it  is  more  rounded  (Fig.  16) 

with  various  appendages  directed  dorsally.     The  abdomen 

of  the  female  is  pointed,  terminating  in  the  ovipositor,  the 

parts  pf  which  as  seen  from  the  side  may  be  together,  or 

widely  separated  dorso-ventrally.     The  genital  glands  can  be 

readily  removed  by  dissecting  as  follows:  Male  grasshoppers, 

which  have  been  chloroformed,  are  opened  by  a  mid- ventral 

incision.     The  abdominal  walls  are  pinned  out  on  a  wax  plate 

under  normal  salt  solution  (0.6  per  cent.).     The  intestinal 

tube,  which  is  usually  black  or  green,  is  taken  out  with  forceps, 

and  the  yellow  or  orange  testes  are  seen  close  together  at  the 

upper  end  of  the  abdomen,  attached  to  the  back.     Each  testis 

consists  of  a  number  of  separate  cylindrical  lobes,  and  it  should 

be  worked  loose  from  the  surrounding  tissue  with  forceps  in 
such  a  way  that  these  lobes  remain  together.  The  tissue 
may  be  preserved  in  Flemming's  strong  solution  or  in  Her- 
mann's fluid,  and  stained  with  iron  haematoxylin. 

Among  the  many  publications  upon  spermatogenesis 
in  the  grasshoppers,  the  following  may  be  cited:  McClung, 
C.  E.,  The  accessory  chromosome — sex  determinant?  Biol. 
Bull.,  1902,  vol.  3,  pp.  43-84;  Sutton,  W.  S.,  On  the  mor- 
phology of  the  chromosome  group  in  Brachystola  magna,  Biol. 
Bull.,  1902,  vol.  4,  pp.  24-39;  McClung,  C.  E.,  The  chromo- 
some complex  of  orthopteran  spermatocytes,  Biol.  Bull., 
1905,  vol.  9,  pp.  304-340;  Robertson,  W.  R.  B.,  The  chromo- 
some complex  of  Syrbula  admirabilis,  Kansas  Univ.  Sci.  Bull., 
1908,  vol.  4,  pp.  273-305;  Davis,  H.  S.,  Spermatogenesis  in 
Acrididae  and  Locustidae,  Bull.  Mus.  Comp.  Zool.,  1908,  vol. 
53>  PP-  57-157;  Wilson,  E.  B.,  The  sex  chromosomes,  Arch, 
fur  mikr.  Anat.,  1911,  vol.  77,  pp.  249-371. 


f 


FIG.  1 6. — DORSAL  (a)  AND 
LATERAL  (b)  VIEWS 
OF  THE  ABDOMEN  OF 
GRASSHOPPERS.  (After 
Hyatt  and  Scudder.) 


—  d 


As  seen  in  sections,  each  lobe  of  the  testis  of  the 
grasshopper  contains  a  considerable  number  of  closed 
sacs  or  cysts,  which  are  filled  with  sexual  cells;  and 
all  the  cells  within  a  cyst  are  in  approximately  the 
same  stage  of  development.  The  cysts  are  shown 
in  Fig.  17,  which  represents  a  longitudinal  section 
of  a  single  lobe.  Usually  the  testis  is  sectioned  as  a 
whole,  and  the  specimen  consists  of  a  group  of  lobes 
cut  transversely  or  obliquely.  Cross  sections  from  the  apical  portion, 
furthest  from  the  outlet,  will  contain  younger  stages  than  the  sections 


FIG.  17. — LOBE  OF  THE 
TESTIS  OF  A  GRASS- 
HOPPER. XSO.  (After 
Davis.) 

a,  apical  cell. 

b,  spermatogonia. 

c,  spermatocytes. 

d,  spermatocytes  dividing. 

e,  spermatids. 

f,  spermatozoa. 


22 


HISTOLOGY 


Spermatogonia 


lower  down  in  the  lobe,  since  the  cysts  form  at  the  apex  and  gradually 
move  downward.  At  the  apex,  according  to  Davis,  there  is  an  apical 
cell  which  is  surrounded  by  young  sexual  cells  known  as  Spermatogonia 
(Fig.  17,  a).  The  spermatogonia  move  away  from  the  apical  cell,  and 
each  becomes  enclosed  in  a  .  cyst-  wall  derived  from  the  surrounding 
tissue.  Within  the  cysts  thus  formed,  the  spermatogonia  multiply,  and 
the  cysts  in  the  upper  part  of  the  lobe  are  rilled  with  spermatogonia 
(Fig.  17,  b).  After  repeated  divisions  the  spermatogonia  pass  through  a 
period  of  growth,  accompanied  by  a  rearrangement  of  their  nuclear  con- 
tents. The  large  cells  with  characteristic  nuclei  which  are  thus  produced, 
are  known  as  primary  Spermatocytes.  They  fill  the  cysts  further  down 
in  ;the  lobe  (Fig.  17,  c).  Each  primary  spermatocyte  divides  into  two 

secondary  Spermatocytes,  and 
each  of  these  divides  into 
two  spermatids,  after  which 
no  further  cell  division  is 
possible  until  fertilization 
takes  place.  But  each  sper- 
matid  becomes  transformed 
from  a  round  cell  into  a  linear 
body  with  a  whip-like  tail, 
and  is  then  capable  of  inde- 
pendent  motion.  Since  in 
this  form  these  cells  were 
once  thought  to  be  parasitic 
animals  living  in  the  sper- 

matlC  fluid,  they  received  the 

1-1,1 
name  SpermatOZOa,  WlilCn  tliCy 

still  retain.1     Cysts  contain- 

ing spermatozoa  occur  near  the  outlet  of  the  lobe,  or  if  the  grasshoppers 
are  collected  late  in  the  season,  they  may  be  found  throughout  most  of  the 
testis.  Specimens  from  young  grasshoppers,  in  which  the  spermatocyte 
divisions  are  abundant,  are  more  desirable,  even  though  no  spermatozoa 
have  become  fully  developed. 

The  succession  of  cell  divisions  described  in  the  preceding  paragraph 
is  shown  in  tabular  form  in  Fig.  18.  Except  for  the  number  of  chromo- 
somes within  the  various  cells,  this  diagram  is  quite  as  applicable  to  man 
as  to  the  grasshopper.  In  this  figure,  however,  only  two  spermatogonial 
divisions  have  been  included.  The  number  of  times  which  the  spermato- 
gonia may  divide  before  becoming  Spermatocytes  is  considerable  and 

1  It  has  been  proposed  to  substitute  the  term  spermium  for  spermatozoon;  and  consequently 
spermiocyte,  spermid,  etc.,  for  spermatocyte  and  spermatid.  The  secondary  Spermatocytes  are 
sometimes  catted  praespermatids  or  praespermids;  but  these  changes  in  names  are  of  questionable 
value. 


Secondary  Spermatocytes 


Spermatozoa 


PIG.  1  8.—  DIAGRAM  OF  THE  CELL  DIVISIONS  IN  SPERMATO- 
GENESIS.  The  figures  indicate  the  number  of  chromo- 
somes  found  in  the  cells  of  certain  grasshoppers. 


SPERMATOGENESIS  23 

presumably  indefinite.  As  seen  in  sections,  the  spermatogonia,  sper- 
matocytes,  and  spermatids  may  be  described  as  follows,  using  for  illus- 
trations Davis's  figures  of  a  common  grasshopper — Dissosteira  Carolina. 

Spermatogonia.  The  nucleus  of  each  spermatogonium  contains  the  full 
number  of  chromosomes,  which  in  most  of  the  grasshoppers  (Acrididae) 
is  23.  With  every  spermatogonial  division,  each  chromosome  is  split 
lengthwise.  In  this  and  other  respects  the  mitotic  figures  are  quite  like 
those  occurring  elsewhere  in  the  body.  They  are  shown  in  Fig.  20,  A, 
B,  and  C.  When  the  twenty- three  chromosomes  have  formed  the  equa- 
torial plate,  it  is  sometimes  possible  to  see  all  of  them  in  a  single  trans- 
verse section  of  the  cell  (Fig.  19,  A).  It  then  appears,  as  found  by  Mont- 
gomery (1901)  in  certain  Hemiptera,  and  a  year  later  by  Button  in  grass- 
hoppers, that  the  chromosomes  vary  in  size,  but  the  "gradations  in  volume 
are  not  between  individual  chromosomes  but  between  pairs,  the  two 
members  of  which  are  of  approximately  equal  size."  In  Fig.  19,  A,  twelve 
forms  of  chromosomes  have  been  identified  by  Davis;  and  all  of  these  are 
paired  except  the  one  numbered  4.  The  members  of  a  pair  are  often,  but 
by  no  means  invariably,  side  by  side.  In  some  cases,  owing  to  foreshort- 
ening, their  resemblance  in  size  is  not  apparent  in  the  drawing.  The  be- 
havior of  the  odd  or  accessory  chromosome  is  of  special  interest,  since  accord- 
ing to  McClung's  hypothesis,  now  well  established,  this  accessory  chromo- 
some is  the  bearer  of  those  qualities  which  determine  sex. 

Primary  spermatocytes.  After  the  last  spermatogonial  division,  the 
cells  begin  their  " growth  period."  At  this  time  the  chromatin  tends  to 
collect  on  one  side  of  the  nucleus,  in  a  condition  known  as  synapsis  (or 
more  recently  as  synizesis).  This  distribution  of  the  chromatin  has  been 
frequently  observed,  but  it  has  not  been  shown  to  be  of  special  signifi- 
cance. In  the  primary  spermatocytes  drawn  in  Fig.  20,  D,  E,  and  F,  the 
chromatin  is  evenly  distributed.  All  of  the  chromosomes,  except  the 
accessory  chromosome,  have  become  filamentous,  but  the  accessory  chro- 
mosome remains  as  a  compact,  darkly  staining  body- close  to  the  nuclear 
membrane.  It  resembles  a  nucleolus,  for  which  in  fact  it  has  been  mis- 
taken. True  nucleoli  may  occur  in  these  cells,  together  with  the  acces- 
sory chromosome,  but  they  stain  differently. 

As  the  primary  spermatocytes  prepare  for  the  next  division,  the  spi- 
reme  becomes  resolved  into  eleven  loops,  each  of  which  represents  the  two 
members  of  a  pair  of  chromosomes  joined  end  to  end.  The  granules  im- 
bedded in  the  liriin  thread  divide  as  usual,  so  that  each  loop  contains  a 
double  row  of  "granules  (Fig.  20,  F).  These  loops  contract  to  form  eleven 
chromosomes,  which,  because  of  their  four  parts,  are  known  as  tetrads. 
The  structure  of  the  tetrads  is  shown  in  Fig.  19,  B-G.  The  filaments  seen 
in  the  upper  row  of  drawings  contract  into  corresponding  solid  forms  of 


24  HISTOLOGY 

chromosomes  seen  in  the  lower  row,  in  which  the  place  of  attachment  to 
the  spindle  fibers  has  been  indicated. 

Each  tetrad  represents  two  chromosomes  joined  end  to  end  and  split 
lengthwise.  The  simplest  forms  are  shown  in  Fig.  19,  B  and  C,  which 
illustrate  respectively  two  ways  in  which  the  tetrad  may  later  divide. 
The  two  component  chromosomes  may  simply  be  pulled  apart,  as  indi- 
cated in  Fig,  19,  B,  in  which  the  spindle  fibers  are  attached  to  the  ends  of 
the  rod.  If  this  takes  place,  each  secondary  spermatocyte  will  receive 
one  member  of  every  pair  of  chromosomes  which  occurred  in  the  sper- 
matogonium,  but  no  part  of  the  other  member.  Such  a  division,  which 
eliminates  one-half  of  the  chromosomes  from  the  daughter  cell,  is  known 
as  a  reductional  division.  The  other  form  of  chromosome  division  is 
known  as  equational.  When  it  takes  place,  every  chromosome  divides 
lengthwise,  and  the  daughter  cells  receive  one-half  of  every  chromosome  in 
the  parent  cell.  This  occurs  in  ordinary  cell  division,  and  also  in  the  di- 
vision of  the  tetrads  provided  that  the  spindle  fibers  are  attached  to  the 
place  where  the  two  component  chromosomes  come  together  (Fig.  19,  C). 


FIG.  19. — A,  POLAR  VIEW  OF  THE  METAPHASE  OF  A  SPERMATOGENIAL  DIVISION  IN  Dissosteira  Carolina. 
XI450  (After  Davis.)  The  pairs  of  chromosomes  have  been  numbered.  B-G,  various  forms  of  tetrads, 
from  primary  spermatocytes.  (After  Davis  and  Robertson.) 

As  a  stage  in  the  separation  of  the  two  halves  of  a  rod-shaped  tetrad,  cross- 
shaped  forms  are  produced  (Fig.  19,  D).  If  the  separation  is  almost 
complete,  such  shapes  are  seen  as  in  Fig.  19,  E.  The  arms  of  the  tetrad 
which  are  not  attached  to  the  spindle  fibers  may  bend  toward  one  another 
and  unite,  so  as  to  form  rings  (F),  or  they  may  twist  about  like  a  figure 
8,  as  shown  in  G.  If  the  spindle  fibers  are  attached  to  the  points  xx  in  the 
upper  figure  in  G,  the  division  will  be  equational;  if  as  shown  in  the  lower 
figure  it  will  be  reductional. 

Usually  it  is  considered  that  the  division  of  the  tetrads  into  double 
bodies  or  dyads,  is  equational,  and  that  the  division  of  the  dyads,  which 
takes  place  when  the  secondary  spermatocytes  divide,  is  reductional. 
According  to  Davis,  however,  the  first  division  of  the  tetrads  is  reductional 
and  the  second  division  is  equational.  In  either  case  the  end-result  is  the 
same.  Each  spermatid  will  contain  one  of  the  four  parts  of  each  tetrad, 
and  thus  one  member  of  every  pair  of  chromosomes  will  be  eliminated  from 
any  given  spermatid. 


SPERMATOGENESIS 


Since  in  the  testis  tetrads  occur  only  in  the  primary  spermatocytes, 
the  cells  shown  in  Fig.  20,  G-J,  are  easily  identified.     These  are  success- 


• 


F 


II 


c 

/ 


ft* 


FIG.  20. — SPERMATOGENESIS  IN  Dissosteira  Carolina.    A-F  X 1450 ;  G-LX  966.     (Davis.) 

A,  B,  C,  prophase,  metaphase,  and  telophase  of  a  spermatogonial  division.    D-L,  successive  stages  in  the 

division  of  a  primary  spermatocyte  into  secondary  spermatocytes. 

ive  stages  in  the  division  of  the  primary  spermatocyte.  In  G  the  accessory 
chromosome  is  seen  as  a  rod-shaped  body  above  and  to  the  right;  in  H  it  is 
below  and  to  the  right.  In  J  it  is  obliquely  placed  just  above  the  equatorial 


26  HISTOLOGY 

plate  and  in  K  it  is  passing  to  the  upper  pole  of  the  spindle.  In  the  sper- 
matogonial  divisions  the  accessory  chromosome  always  divides  with  the 
others;  but  in  the  division  of  the  primary  spermatocyte  it  passes  un- 
divided into  one  of  the  daughter  cells.  Thus  one  secondary  spermatocyte 
will  receive  eleven  chromosomes  (dyads)  and  the  other  will  receive  twelve 
(eleven  dyads  and  the  accessory  chromosome) .  In  the  late  anaphase  shown 
in  Fig.  20,  L,  the  accessory  chromosome  cannot  be  recognized. 

Secondary  spermatocytes.  The  secondary  spermatocytes  pass  rapidly 
from  the  condition  shown  in  Fig.  20,  L,  to  that  of  Fig.  21,  A.  A  nuclear 
membrane  has  developed,  and  the  dyads  have  become  somewhat  filamen- 
tous. Without  passing  through  a  complete  resting  stage  they  proceed  to 
divide  as  shown  in  Fig.  21,  B-F.  The  dyads  separate  into  their  com- 
ponent halves.  In  those  secondary  spermatocytes  which  received  the 
accessory  chromosome,  that  body  will  be  seen  dividing  with  the  dyads,  and 
each  spermatid  will  receive  one-half  of  it.  It  has  been  questioned  whether 
the  division  of  the  accessory  chromosome  is  longitudinal  and  there- 
fore equational,  or  transverse  and  reductional.  Many  cytologists 
consider  that  if  a  chromosome  splits  lengthwise,  all  of  its  parts  will  be 
represented  in  the  resulting  halves,  but  if  it  divides  transversely,  essential 
elements  will  be  lost.  This  conception  lends  importance  to  the  question 
of  transverse  or  longitudinal  division  of  the  accessory  chromosome.  By 
the  division  of  this  chromosome  it  comes  about  that  one-half  of  the  sper- 
matids  contain  twelve  chromosomes,  and  one-half  contain  eleven,  as  indi- 
cated in  the  diagram,  Fig.  18.  The  spermatids  shown  in  Fig.  21,  F,  con- 
tain the  accessory  chromosome. 

Spermatids  and  Spermatozoa,  In  forming  spermatozoa,  the  spermatids 
become  elongated,  passing  from  the  condition  shown  in  Fig.  21,  F,  to  that 
of  Fig.  21,  G.  The  chromatin  within  the  nucleus  is  distributed  in  fine 
granules  throughout  the  linin  reticulum.  Close  to  the  nuclear  mem- 
brane a  small  dark  body  has  appeared,  from  which  a  slender  filament  has 
grown  out.  This  body  is  usually  described  as  the  centrosome.  A  conden- 
sation within  the  cytoplasm,  seen  also  in  F,  is  known  as  the  paranucleus. 
It  is  of  uncertain  origin,  but  may  proceed  from  the  cytoplasmic  structure 
called  mitochondrium.  The  paranucleus  forms  a  sheath  about  the  axial 
filament. 

Successively  later  stages  are  shown  in  Fig.  21,  H,  I,  and  J.  The  chro- 
matin within  the  nucleus  becomes  homogeneous  and  very  dense;  at  the 
same  time  the  nucleus  elongates  and  forms  the  head  of  the  spermatozoon. 
This  is  enveloped  by  the  cell  membrane,  but  there  is  no  appreciable  layer 
of  protoplasm  around  it.  The  centrosome  elongates  and  forms  the  middle 
piece  of  the  spermatozoon;  and  the  axial  filament,  with  a  covering  derived 
from  the  paranucleus  and  cytoplasm,  constitutes  the  tail.  Only  a  portion 
of  the  tail  is  included  in  the  figure.  The  human  spermatozoon  likewise 


SPERMATOGENESIS 


consists  of  a  head,  which  is  essentially  the  nucleus,  a  middle  piece  containing 
the  centrosome,  and  a  tail ;  but  the  form  of  the  head  is  very  different  from 


PIG.  21. — SPERMATOGENESIS    IN    Dissosteita    Carolina.     X 1450.     (Davis.) 

A-F,  successive  stages  in  the  division  of  a  secondary  spermatocyte  into  spermatids.     G— J,  successive  stages 
in  the  transformation  of  spermatids  into  spermatozoa. 

that  in  the  grasshopper.     It  will  be  described  in  a  later  chapter. 

Although  the  spermatozoa  of  the  grasshopper  appear  alike,  it  has  been 
shown  that  one-half  of  them  contain  eleven  chromosomes,  and  one-half 


28  HISTOLOGY 

contain  twelve.  The  mature  ova  all  contain  twelve  chromosomes.  If  a 
spermatozoon  with  eleven  chromosomes  unites  with  an  ovum  with  twelve, 
a  male  animal  will  be  produced,  in  every  cell  of  which  there  will  be  twenty- 
three  chromosomes.  But  if  the  spermatozoon  contains  twelve  chromo- 
somes, a  female  animal  is  formed,  containing  twenty-four  chromosomes 
in  every  cell.  Thus  sex  appears  to  be  determined  by  the  presence  or 
absence  of  a  chromosome  within  the  spermatozoon. 

In  some  cases,  as  in  several  Hemiptera  described  by  Wilson,  the  acces- 
sory chromosome  is  paired,  but  its  mate  is  of  small  size.  Thus  the  sperma- 
tozoa all  have  the  same  number  of  chromosomes;  but  half  of  them  contain 
the  large  member  of  the  pair  and  will  produce  females,  and  the  other  half 
contain  the  small  member  and  will  produce  males.  The  mature  ova  all 
contain  the  large  member.  In  these  insects,  therefore,  both  sexes  con- 
tain the  same  number  of  chromosomes,  but  the  cells  of  the  male  contain 
a  ,small  chromosome,  whereas  the  corresponding  one  in  the  female  is 
large.  From  these  observations  it  is  reasonable  to  conclude  that  sex  may 
be  determined  by  a  difference  in  the  nature  of  certain  chromosomes,  in 
those  animals  in  which  there  are  no  appreciable  differences  in  size  or 
number. 

In  man,  a  difference  in  the  number  of  chromosomes  in  the  sexes  has 
been  reported,  but  the  observations  have  not  been  confirmed.  It  is  sup- 
posed that  the  spermatogonia  contain  twenty-four  chromosomes,  but  it 
has  not  been  shown  that  they  exist  as  pairs.  The  spermatocytes,  sperma- 
tids  and  spermatozoa  apparently  contain  twelve.  As  the  principal  con- 
stituents of  the  spermatozoon,  the  chromosomes  are  believed  to  be  the 
essential  agents  in  the  transmission  of  all  qualities  inherited  from  the  male 
parent,  and  certain  of  them  may  determine  sex. 


OOGENESIS. 

Mature  ova  result  from  a  succession  of  cell  divisions  closely  comparable 
with  those  which  produce  spermatozoa.  The  primitive  female  sexual 
cells  correspond  with  the  spermatogonia,  and  are  called  oogonia.  They 
are  provided  with  the  full  number  of  chromosomes,  and  divide  an  indefi- 
nite number  of  times.  After  a  period  of  growth  they  become  primary 
oocytes,  in  which  the  number  of  chromosomes  is  reduced  one-half.  The 
primary  oocytes  divide  to  form  secondary  oocytes;  and  these  again  divide 
to  produce  the  mature  ova,  which  are  incapable  of  further  division 
unless  fertilization  takes  place.  (The  term  ovum  is  ordinarily  loosely 
applied,  so  that  it  includes  not  only  the  mature  cells,  but  also  oocytes, 
and  the  clusters  of  cells  resulting  from  the  division  of  the  fertilized  ovum.) 

Although  the  mature  ovum  and  the  spermatozoon  are  closely  similar 


OOGENESIS  29 

in  their  nuclear  constitution,  they  differ  radically  as  to  form,  size,  and  cyto- 
plasmic  structure.  The  ova  are  very  large  cells,  stored  with  nutriment 
for  the  embryo  which  each  one  may  later  produce.  In  the  higher  verte- 
brates they  are  formed  in  relatively  small  numbers.  According  to  Hen- 
sen's  estimate,  about  two  hundred,  ready  for  fertilization,  are  produced 
by  the  human  female  in  a  life-time.  But  the  male,  according  to  Lode, 
produces  340  billion  spermatozoa,  or,  as  stated  by  Waldeyer,  nearly  850 
million  per  ovum.  A  large  number  must  be  produced,  since  many  will 
fail  to  traverse  the  uterus  and  tube  so  as  to  find  the  ovum  at  the  time  of 
its  discharge  from  the  ovary.  The  ova  of  lower  vertebrates,  which 
are  fertilized  and  develop  outside  of  the  body,  are  discharged  in  great 
numbers;  in  certain  fishes  from  three  to  four  million  are  produced 
annually. 

The  multiplication  of  oogonia  in  the  human  ovary  takes  place  before 
birth,  and  about  fifty  thousand  are  produced.  At  birth,  or  shortly  there- 
after, all  the*o6gonia  have  become  primary  oocytes  (Keibel).  At  first  the 
oocytes  are  small,  but  they  enlarge  at  varying  rates,  and  the  largest  are 
indistinguishable  from  mature  ova  except  by  their  nuclear  contents.  Since 
some  grow  more  rapidly  than  others,  the  ovary  in  childhood  contains 
primary  oocytes  of  many  sizes.  Each  oocyte  becomes  enclosed  in  a  cyst 
or  follicle.  The  way  in  which  these  follicles  develop,  and  the  manner  in 
which  the  oocyte  escapes  into  the  uterine  tube  by  the  rupture  of  these 
follicles,  will  be  described  in  connection  with  the  ovary.  Between  the  cells 
of  the  follicle  and  the  oocyte,  there  is  a  broad,  radially  striated  membrane, 
known  as  the  zona  pellucida  or  zona  radiata  (Fig.  22).  This  zona  has  some- 
times been  regarded  as  a  cell  membrane,  but  the  oocyte  divides  within  it  as 
if  enclosed  in  a  capsule.  It  does  not  invest  the  daughter  cells  like  a  mem- 
brane. The  radial  striations  have  been  interpreted  as  slender  canals 
containing  processes  of  the  f  ollicular  cells,  and  the  zona  has  been  considered 
as  a  product  of  these  cells.  In  certain  cases  a  perivitelline  space  has  been 
described  as  encircling  the  oocyte  and  thus  separating  it  from  the  zona, 
but  this  space  has  b.een  considered  as  artificial,  or  as  a  refractive  line 
wrongly  interpreted  as  a  space. 

The  cytoplasm  of  the  oocyte  becomes  charged  with  yolk  granules  or 
spherules.  They  constitute  the  deutero plasm  (or  deutoplasm),  but  this 
term  is  equally  applicable  to  fat  droplets  and  other  secondary  products  of 
the  protoplasm.  In  the  human  oocyte  the  granules  are  centrally  placed 
(Fig.  22),  and  they  are  so  transparent,  when  fresh,  as  to  cause  only  a  slight 
opacity.  In  the  eggs  of  many  animals  the  yolk  is  more  highly  developed, 
and  it  may  be  evenly  distributed  or  gathered  at  one  pole.  Within  the 
cytoplasm  of  the  developing  oocyte,  a  large  dark  body  of  radiate  structure 
is  sometimes  conspicuous.  It  is  inappropriately  known  as  the  yolk  nucleus, 
and  is  probably  a  derivative  of  the  centrosome  and  surrounding  archo- 


30  HISTOLOGY 

plasm.     Other  "vitelline  bodies,"  of  uncertain  origin  and  significance, 
have  been  described.     Some  have  been  considered  as  nuclear  extrusions. 

The  nucleus  of  the  oocyte  is  very  large  and  vesicular.  The  chromatin 
occurs  chiefly  along  the  nuclear  membrane  and  about  the  nucleolus.  The 
nucleolus  is  also  very  large,  and  Nagel  stated  that  in  the  fresh  condition  it 
exhibits  amoeboid  movements,  but  this  observation  has  not  been  verified. 
The  nuclei  of  the  oocytes  ordinarily  show  no  signs  of  mitosis,  and  they 
may  remain  in  the  resting  condition  for  thirty  years  or  more  and  then  di- 
vide. Many  of  them,  however,  will  degenerate  without  division. 


FIG.  22.— THE  OVUM  AS  DISCHARGED  FROM  A  VESICULAR  FOLLICLE  OF  AN  EXCISED  OVARY  OF  A  WOMAN 

THIRTY  YEARS  OF  AGE.    Examined  fresh  in  the  liquor  folliculi.    (Nagel.) 

c.  r.,  Corona  radiata  composed  of  cells  of  the  follicle;  n.,  nucleus;  p.,  granular  protoplasm;  p.  s.,  perivitel- 
hne  space;  y.,  yolk;  z.  p.,  zona  pellucida.     (From   McMurrich's  "Embryology.") 

The  cell  divisions  which  give  rise  to  the  secondary  oocyte  and  the  ma- 
ture ovum  respectively,  have  never  been  observed  in  man.  Some  of  the 
cells  within  the  ovary  may  be  secondary  oocytes  and  the  cell  shown  in  Fig. 
22  may  be  of  this  sort,  or  possibly  a  mature  ovum,  but  this  cannot  be  de- 
termined. From  what  is  known  of  other  mammals,  however,  it  may  con- 
fidently be  assumed  that  the  cell  divisions  take  place  as  shown  in  the  dia- 
gram, Fig.  23. 

When  the  primary  oocyte  divides,  the  chromosomes,  reduced  in  number, 
also  divide  and  are  equally  distributed  to  the  daughter  cells;  but  the  great 
mass  of  cytoplasm  remains  with  one  of  these  cells,  namely,  the  secondary 


OOGENESIS  31 

oocyte.  The  other  cell,  which  is  relatively  very  small,  is  known  as  the 
first  polar  body,  or  polar  cell.  It  has  the  same  nuclear  contents  as  the  sec- 
ondary oocyte,  and  may  divide  into  two  other  polar  bodies,  equivalent  to 
mature  ova.  More  often  it  degenerates  without  division.  When  the 
secondary  oocyte  divides,  it  likewise  produces  one  large  cell,  the  mature 
ovum,  and  one  small  cell,  the  second  polar  body.  The  latter  is  said  to  be  cap- 
able of  fertilization,  but  to  what  extent  it  may  develop  is  unknown. 
Functionally  the  production  of  polar  bodies  serves  to  prevent  the  sub- 
division and  distribution  of  the  nutritive  material  elaborated  within  the 
primary  oocyte.  One  mature  ovum  with  abundant  yolk  is  provided  at 
the  expense  of  three  ova  (polar  bodies)  which  degenerate. 

Although  the  maturation  of  the  ovum  has  not  been  observed  in  man, 
nor  even  the  presence  of  definite  polar  bodies,  the  entire  process  has  been 


Oogonia 


Secondary  Oocyte 
Polar  Bodies 

Mature  Ovum 
FIG.  23. — DIAGRAM  OF  THE  CELL  DIVISIONS  IN  OOGENESIS.     (Compare  with  Fig.  18.) 

carefully  studied  in  other  mammals,  notably  in  the  mouse.1  It  has  been 
shown  that  the  maturation  of  the  ovum  of  the  mouse  takes  place  rapidly, 
both  of  the  oocyte  divisions  being  accomplished  within  from  four  to  fifteen 
hours.  The  first  polar  body  usually  forms  before  the  oocyte  is  discharged 
from  the  ovarian  follicle — in  other  words,  before  ovulation  takes  place. 
The  second  polar  body  is  usually  formed  in  the  uterine  tube,  after  the  sper- 
matozoon has  entered  the  oocyte.  Long  and  Mark  have  found  that  the 
chromosomes  of  the  primary  oocyte  are  tetrads,  or  bodies  showing  trans- 
verse and  longitudinal  divisions;  and  that  those  of  the  secondary  oocyte  are 
dyads.  They  believe  that  the  first  division  is  transverse  or  reductional, 
and  that  the  second  is  equational. 

1  Among  the  most  important  papers  are:  Sobotta,  J.,  Die  Befruchtung  und  Furchung  des 
Eies  der  Maus.  Arch.  mikr.  Anat.,  1895,  vol.  45,  pp.  15-91. 

Long,  J.  A.,  and  Mark,  E.  L.  The  maturation  of  the  egg  of  the  mouse.  Carnegie  Inst. 
Publ.  No.  142,  1911,  pp.  1-72. 


32  HISTOLOGY 

The  difficulty  of  counting  chromosomes  is  apparent  from  the  varying 
numbers  which  have  been  reported  in  the  mouse.  After  reduction  the 
number  has  been  placed  at  8,  12,  16,  18  and  20  by  different  observers. 

The  polar  bodies  in  the  mouse  are  relatively  large.  In  the  upper  part 
of  Fig.  24,  A,  a  polar  body  is  about  to  be  formed,  and  it  is  completely  cut 
off  from  the  oocyte  in  Fig.  24,  C.  In  D  and  G,  two  polar  bodies  are  shown. 

FERTILIZATION. 

In  the  mouse,  from  six  to  ten  hours  after  coitus,  spermatozoa  have  made 
their  way  to  the  distal  end  of  the  uterine  tube,  where  fertilization  takes 
place.  According  to  Long  and  Mark,  the  maturation  of  ova  usually  occurs 
at  some  time  during  the  period  from  "  13!  to  28^  hours"  after  the  mo  use  has 
given  birth  to  a  litter;  and  during  the  process  of  their  maturation,  the 
oocytes  are  discharged  from  the  ovary  and  enter  the  distal  end  of  the  tube. 
Here,  if  fertilization  takes  place,  a  single  spermatozoon  penetrates  the  zona 
pellucida.  In  a  section  obtained  by  Sobotta,  the  entrance  of  the  sperma- 
tozoon has  been  partially  accomplished  (Fig.  24,  B).  Its  tail  lies  outside 
of  the  zona,  and  appears  to  have  become  thickened.  In  another  specimen 
Sobotta  found  the  head,  middle  piece  and  a  part  of  the  tail  within  the 
cytoplasm  of  the  oocyte.  The  tail  had  broken  as  it  crossed  the  zona,  and 
the  portion  remaining  outside  had  drawn  together  and  was  disintegrating. 
In  some  animals  it  is  said  that  the  entire  spermatozoon  enters  the  ovum, 
but  in  others  only  the  head  and  middle  piece.  In  any  case  the  tail  appears 
to  be  a  propelling  apparatus  which  becomes  functionless  after  the  head 
and  middle  piece  have  passed  through  the  zona.  It  has  entirely  disap- 
peared in  the  stage  shown  in  Fig.  24,  A,  in  which  the  head  of  the  spermato- 
zoon is  seen  within  the  oocyte  on  the  right  side  of  the  figure.  Meanwhile 
the  oocyte  is  becoming  a  mature  ovum  by  undergoing  divisions  and  pro- 
ducing the  second  polar  body;  and  the  anaphase  of  this  division  is  shown  in 
Fig.  24,  A.  Sobotta  stated  that  no  centrosomes  occur  in  connection  with 
the  spindles  of  the  maturation  divisions,  and  Long  and  Mark  have  like- 
wise failed  to  find  any  "typical  centrosomes." 

In  Fig.  24,  C,  the  second  .polar  body  has  become  a  separate  cell.  The 
chromosomes  of  the  ovum,  which  is  now  mature,  have  formed  a  compact 
mass.  They  next  become  resolved  into  a  chromatic  reticulum,  and  a 
resting  nucleus  is  produced,  provided  with  a  nuclear  wall  and  distinct  nu- 
cleoli  (Fig.  24,  D  and  E).  This  nucleus,  which  becomes  large  and  moves 
toward  the  center  of  the  cell,  is  known  as  the  female  pronucleus.  Mean- 
while the  head  of  the  spermatozoon  has  enlarged  and  formed  the  male 
pronucleus,  as  shown  in  Fig.  24,  C,  D  and  E. 

The  two  pronuclei,  which  are  very  similar,  develop  rapidly,  "  probably 
within  a  few  minutes  after  the  entrance  of  the  spermatozoon."  Simul- 
taneously they  prepare  for  division,  and  the  chromatic  reticulum  of  each 


FERTILIZATION 


33 


becomes  resolved  into  the  reduced  number  of  chromosomes  which  it  re- 
ceived during  maturation  (Fig.  24,  F).  A  centrosome  with  astral  radia- 
tions is  now  seen  between  the  two  groups.  In  Fig.  24,  G,  it  has  divided 
in  two,  and  the  spindle  has  developed.  There  has  been  much  discussion 
as  to  the  origin  of  these  centrosomes.  Since  in  this  case  they  arise  by  the 
division  of  a  single  body,  the  possibility  that  one  comes  from  the  sper- 


0 


11  f  J 

FIG.  24.— MATURATION  AND  FERTILIZATION  OF   THE  OVUM  OF  THE  MOUSE.     A,C-J,Xsoo;  BX7SO. 

(After  Sobotta.) 

A-C,  entrance   of   the   spermatozoon  and  formation  of  the  second  polar  body.     D-E,  development 
of  the  pronuclei.     F— J,  successive  stages  in  the  first  division  of  the  fertilized  ovum. 

matozoon  and  one  from  the  ovum  has  been  eliminated.  Moreover  in  the 
mouse  they  cannot  be  derived  from  the  surviving  centrosome  of  the  last 
maturation  division  of  the  ovum,  for  that  division  takes  place  without 
centrosomes.  Therefore  the  centrosome  must  either  be  brought  in  by  the 
spermatozoon  as  a  constituent  of  its  middle  piece,  or  it  must  be  a  new  forma- 
tion. Sobotta  accepted  the  former  alternative,  and  he  observed  a  centro- 

3 


34 


HISTOLOGY 


some  in  connection  with  the  head  of  the  spermatozoon  in  certain  stages 
(Fig.  24,  C)  but  not  in  all.  It  is  probable,  according  to  Conklin,  that 
"the  source  of  the  cleavage  centrosomes  may  differ  in  different  animals, 
or  even  in  the  same  animal  under  different  conditions." 

Later  stages  in  the  division  or  "cleavage"  of  the  fertilized  ovum  into 
two  cells  are  shown  in  Fig.  24,  H-J.  The  two  groups  of  chromosomes 
come  together  upon  the  spindle  so  that  the  full  number,  characteristic 
of  the  species,  is  restored.  Each  chromosome  then  divides  lengthwise, 
and  thus  each  daughter  cell  receives  one-half  of  its  chromosomes  from 
the  male  parent  and  one-half  from  the  female  parent.  This  is  strikingly 
evident  when  the  eggs  of  the  fish  Fundulus,  which  have  long  rod-shaped 
chromosomes,  are  fertilized  with  the  sperm  of  Menidia,  which  has  shorter 
rods.  Moenkhaus,  who  performed  this  experiment  (Amer.  Journ 
Anat,  1904,  vol.  3,  pp.  29-64),  states  that  the  two  kinds  of  chromosomes 
remain  grouped  and  bilaterally  distributed  on  the  spindles  during  the  first 
and  second  divisions  of  the  fertilized  ovum,  but  that  later  they  become 
gradually  mingled. 

Important  information  in  regard  to  the  nature  of  fertilization  has 
been  obtained  by  experiments  upon  unfertilized  eggs.  Changes  in  the 
concentration  or  composition  of  the  sea  water  in  which  the  eggs  of  marine 
animals  have  been  placed,  mechanical  agitation,  or,  in  the  case  of  frogs' 
eggs,  puncturing  the  outer  layer  with  a  needle,  have  led  to  repeated  cell 
divisions.  In  this  way  embryos  or  larvae  have  been  produced  from 
unfertilized  eggs,  and,  in  a  few  instances,  adult  animals.  Loeb,  who 
has  been  a  foremost  investigator  in  this  field,  concludes  that  the  sperma- 
tozoon causes  the  development  of  the  egg  by  carrying  a  substance  into 
it  which  liquefies  the  cortical  layer  of  the  egg,  and  thereby  causes  the 
formation  of  a  membrane.  "This  membrane  formation,  or  rather  the 
modification  of  the  surface  of  the  egg  which  underlies  the  membrane 
formation,  starts  the  development."  At  the  same  time  there  is  an  accelera- 
tion of  the  oxidations  in  the  egg.  "What  remains  unknown  at  present 
is  the  way  in  which  the  destruction  of  the  cortical  layer  of  the  egg  accel- 
erates the  oxidations." 

For  the  physicist  and  chemist,  the  production  of  mitotic  figures 
and  the  process  of  fertilization,  have  been  subjects  of  great  interest,  and 
discussions  of  their  significance  will  be  found  in  various  text-books  of 
physiology  and  biological  chemistry.  For  further  morphological  details 
the  student  is  referred  to  "The  Cell  in  Development  and  Inheritance," 
by  E.  B.  Wilson  (2nd  ed.,  New  York,  1900)  and  to  the  chapters  on  "Die 
Geschlechtszellen"  and  "Eireife,  Befruchtung  und  Furchungsprozess," 
by  W.  Waldeyer  and  R.  Hertwig  respectively,  in  vol.  i  of  Hertwig's 
"Handbuch  der  vergl.  u.  exp.  Entwickelungslehre  der  Wirbeltiere," 
(Jena,  1906). 


II.     GENERAL  HISTOLOGY. 
HISTOGENESIS. 

SEGMENTATION  AND  THE  FORMATION  or  THE  GERM  LAYERS. 

The  body  is  composed  of  groups  of  similarly  differentiated  cells,  similar 
therefore  in  form  and  function.  Such  groups  are  known  as  tissues.  His- 
tology (Greek,  IO-TO'S,  "a  textile  fabric")  is  the  science  of  tissues,  and  his- 
togenesis  deals  with  their  origin.  There  are  as  many  tissues  in  the  body  as 
there  are  "sorts  of  substance";  thus  the  liver  consists  essentially  of  hepatic 
tissue,  and  the  bones  of  osseous  tissue.  All  of  these,  however,  are  modifica- 
tions of  a  small  number  of  fundamental  tissues,  the  development  of  which 
may  now  be  considered. 

It  has  already  been  stated  that  a  new  individual  begins  existence  as  a 
single  cell,  the  fertilized  ovum.  This  cell  then  divides  by  mitosis  into  a 
pair  of  cells,  Fig.  25,  A;  and  these  again  divide,  making  a  group  of  four, 
Fig.  25,  B.  By  repeated  mitosis  a  mass  of  cells  is  produced,  which  because 
of  its  resemblance  to  a  mulberry,  is  called  a  morula  (Fig.  25,  C).  Develop- 
ment to  this  point  is  known  as  the  segmentation  of  the  ovum. 

A  section  through  the  morula  of  the  rabbit  is  shown  in  Fig.  25,  D.  An 
outer  layer  of  cells  surrounds  the  inner  cell  mass.  Soon  a  cup-shaped 
cleft,  crescentic  in  vertical  section,  forms  between  the  outer  and  inner 
cells  as  shown  in  E,  and  this  cleft  enlarges  until  the  entire  structure  becomes 
a  thin-walled  vesicle,  within  and  attached  to  one  pole  of  which  is  the  inner 
cell  mass  (Fig.  25,  F).  Cells  from  this  mass  gradually  spread  beneath 
the  outer  layer  until  they  form  a  complete  lining  for  the  vesicle.  The 
inner  layer  is  called  entoderm,  and  the  outer  layer  ectoderm. 

Before  the  entoderm  has  encircled  the  vesicle,  a  third  layer  has  appeared 
between  the  other  two.  This  middle  layer  is  the  mesoderm  (Fig.  25, 
G).  It  arises  from  the  place  where  the  ectoderm  and  entoderm  blend 
with  one  another.  The  layers  may  be  separated  and  floated  apart 
except  at  this  spot  where  they  are  "tied  together."  This  place  is  there- 
fore called  the  primitive  knot.  The  mesoderm  also  spreads  laterally  from 
a  longitudinal  thickening  of  the  ectoderm,  which  extends  backward  from 
the  primitive  knot  and  marks  out  the  future  longitudinal  axis  of  the 
embryo.  This  thickening  is  the  primitive  streak.  Arising  from  the  primi- 
tive knot  and  primitive  streak,  the  mesoderm  spreads  out  rapidly  between 
the  ectoderm  and  entoderm,  and  very  soon  it  splits  into  two  layers  (Fig. 
25,  H).  One  of  them  (the  somatic  layer)  is  closely  applied  to  the  ecto- 

35 


36  HISTOLOGY 

derm,  and  the  other  (the  splanchnic  layer)  to  the  entoderm.  Between 
them  is  a  cavity,  known  as  the  body  cavity  or  coslom,  which  in  the  adult 
becomes  subdivided  into  the  peritoneal,  pleural,  and  pericardial  cavities. 
The  ectoderm  and  the  somatic  mesoderm  together  form  the  body  wall  or 
somatopleure;  the  entoderm  and  the  splanchnic  mesoderm  together  form 
the  intestinal  wall  or  splanchnopleure. 

Reviewing  the  preceding  paragraphs  it  is  seen  that  the  fertilized  ovum, 
through  segmentation,  forms  a  morula,  which  later  becomes  a  vesicle 
composed  of  three  germ  layers,  the  outer  or  ectoderm,  inner  or  entoderm, 
and  middle  or  mesoderm.  By  the  folding  of  these  layers  the  body  as  a 
whole  acquires  its  form;  and  by  their  growth  and  differentiation  all  the 
organs  and  tissues  are  produced,  together  with  the  fetal  membranes  which 
surround  the  embryo.  Omitting  for  the  present  all  reference  to  the  mem- 
branes, the  fundamental  changes  which  the  germ  layers  undergo  may  be 
briefly  considered,  as  follows : 

Ectoderm.  A  portion  of  the  ectoderm  forms  a  layer  of  cells  covering 
the  body  of  the  embryo.  In  the  adult  this  becomes  the  outer  layer  of 
the  skin,  or  the  epidermis,  and  from  it,  hairs,  nails  and  the  mammary, 
sebaceous  and  sweat  glands  develop.  It  is  reflected  under  the  eyelids 
and  over  the  front  of  the  eye,  and  forms  the  lachrymal  glands.  It  etxends 
into  the  external  auditory  opening  and  there  forms  the  ceruminous  glands; 
and  into  the  nasal,  oral,  anal  and  urogenital  apertures.  Within  the 
mouth  it  forms  the  salivary  glands,  the  enamel  of  the  teeth,  and  the  cells 
associated  with  the  sense  of  taste.  Thus  it  extends  far  back  toward 
the  pharynx,  and  dorsally,  in  its  deepest  part,  it  produces  the  anterior 
lobe  of  the  hypophysis,  which  will  be  described  in  a  later  chapter.  In 
the  nose  it  also  extends  far  inward,  so  that  it  lines  the  accessory  cavities 
which  push  out  from  the  nasal  cavity  into  certain  bones  of  the  head,  and 
it  forms  the  olfactory  cells.  An  inpocketing  of  the  ectoderm  produces 
the  lining  of  the  deep  portion  of  the  ear,  including  the  auditory  cells,  and, 
as  will  be  seen,  the  ectoderm  gives  rise  to  .the  lens  and  retina  of  the  eye. 
Thus  the  ectoderm  not  only  forms  the  outer  covering  of  the  body,  with 
extensions  into  the  several  apertures,  but  it  produces  various  sensory 
cells  which  are  stimulated  from  external  sources. 

The  second  great  derivative  of  the  ectoderm  is  the  nervous  system. 
It  arises  in  young  embryos  as  the  medullary  groove.  This  is  a  longitudinal 
groove  or  furrow,  situated  in  front  of  the  primitive  knot  and  appearing 
in  cross  section  as  a  median  dorsal  depression  (Fig.  25,  G  and  H).  Later 
th,e  groove  becomes  a  tube  by  the  coalescence  of  its  dorsal  edges,  which 
are  about  to  unite  in  Fig.  25,  H.  The  tube  then  becomes  completely 
separated  from  the  epidermal  layer  of  ectoderm,  as  in  Fig.  29. 

The  closure  of  the  medullary  groove  to  form  a  tube  begins  near  the 
anterior  end  of  the  embryo  and  proceeds  backward.  Thus  for  a  time  the 


GERM   LAYERS 


37 


tube  opens  to  the  exterior  both  anteriorly,  at  the  anterior  neuropore,  and 
posteriorly,  at  the  posterior  neuropore.  Eventually  the  neuropores  become 
closed  over,  and  the  tube  is  then  wholly  detached  from  the  epidermal 
layer.  The  form  of  the  tube  is  shown  in  Fig.  27,  which  represents  a  dis- 
sected reconstruction  of  a  chick  embryo.  In  this  dissection  the  epidermal 
layer,  which  covers  the  upper  or  dorsal  surface  of  the  embryo,  has  been 
almost  all  removed.  A  portion  of  it  which  forms  a  fold  under  the  head 
and  around  the  anterior  neuropore  has  been  left  in  place,  and  also  a  por- 
tion around  the  rhomboidal  sinus,  which  may  be  regarded  as  an  expanded 
posterior  neuropore.  By  removing  the  epidermal  layer,  the  medullary 
tube  has  been  exposed.  Anteriorly  it  shows  a  succession  of  expansions 


D 


E 


ir 


(A-E. 


FIG.  25. — SEGMENTATION  OF  THE  OVUM  AND  FORMATION  OF  THE  GERM  LAYERS  IN  THE  RABBIT. 
after  van  Beneden;  F-H,  after  Duval.) 

A-C  represent  surface  views  of  the  two-cell  stage,  four-cell  stage  and  morula  respectively.  D-H  are  verti- 
cal sections.  In  D  and  E  the  inner  cell  mass  is  heavily  shaded.  Ect.,  ectoderm.  Ent.,  entoderm. 
Mes.,  mesoderm. 

which  are  to  form  the  brain,  and  also  a  pair  of  lateral  outpocke tings,  or 
optic  vesicles,  each  of  which  will  become  the  retina  of  an  eye.  Posteriorly 
the  tube  is  slender,  and  this  part  becomes  the  spinal  cord.  The  brain 
and  spinal  cord,  which  are  derived  directly  from  the  medullary  tube, 
constitute  the  central  nervous  system.  The  peripheral  nervous  system 
consists  of  bundles  of  nerve  fibers  which  ramify  throughout  the  body, 
together  with  masses  of  nerve  cells  associated  with  these  fibers.  The 
nerve  cells  are  detached  ectodermal  cells,  arising  chiefly  from  the  dorsal 
part  of  the  medullary  groove,  and  the  fibers  are  protoplasmic  outgrowths 
of  these  detached  cells  and  of  others  which  remain  in  the  wall  of  themedul- 


38  HISTOLOGY 

lary  tube.     Thus  the  entire  nervous  system,  central  and  peripheral,  is 
ectodermal  in  origin. 

Entoderm.  Before  considering  the  chief  derivatives  of  the  entoderm, 
the  notochord  (or  chorda  dorsalis)  may  be  briefly  described.  In  the 
lowest  vertebrates  it  is  an  important  supporting  structure,  and  is  regarded 
as  "the  primitive  forerunner  of  the  vertebral  column."  It  arises  in 
young  mammalian  embryos  as  a  median  longitudinal  band  of  cells  in 
the  entodermal  layer,  immediately  below  the  floor  of  the  medullary  groove. 
In  the  diagram,  Fig.  25,  H,  it  is  shown  as  an  elevation;  in  Fig.  29,  it  ap- 
pears as  a  group  of  cells  completely  detached  from  the  underlying  ento- 
derm. It  then  forms  a  longitudinal  rod  extending  forward  from  the  primi- 
tive knot  to  the  under  side  of  the  brain,  as  seen  in  the  longitudinal 
section  of  the  chick  embryo,  Fig.  28.  Later  it  becomes  surrounded  by 
mesodermal  cells,  which  develop  into  the  bodies  (or  centra)  of  the  verte- 
brae together  with  the  intervertebral  ligaments  between  them.  These  are 


Nch. 


Nch. 


FIG.  26. — THE  NOTOCHORD. 
A,  in  a  sheep  embryo  of  14.6  mm.  (after  Minot);  B,  in  a  cod  fish;  C,  in  man  (after  Dwight). 

shown  in  Fig.  26,  A,  as  alternating  light  and  dark  areas  respectively.  The 
notochord  in  passing  through  them  shows  " segmental  flexures "  (Minot). 
In  the  vertebral  column  of  a  fish  (Fig.  26,  B)  the  central  notochordal 
rod  has  expanded  between  the  bodies  of  the  vertebrae  so  as  to  form  large 
lenticular  masses  of  gelatinous  pulp.  These  retain  a  very  slender  con- 
nection with  one  another.  In  the  human  adult,  the  notochord  is  repre- 
sented by  the  series  of  detached  expansions,  or  nuclei  pulposi,  one  of  which 
occurs  in  each  intervertebral  ligament  (Fig.  26,  C).  These  nuclei  are 
composed  of  a  peculiar  tissue,  the  development  of  which  has  been  de- 
scribed by  L.  W.  Williams  (Amer.  Journ.  Anat.,  1908,  vol.  8,  pp.  251- 
284).  The  notochord  is  very  rarely  the  source  of  tumors.  Occasionally, 
owing  to  its  connection  with  the  entoderm,  which  is  retained  longest 
anteriorly,  it  gives  rise  to  a  pharyngeal  recess  (Huber,  Anat.  Record, 
1912,  vol.  6,  pp.  373-404). 


GERM    LAYERS  39 

In  young  mammalian  embryos  the  entire  entoderm,  with  the  noto- 
chordal  cells  included  in  its  dorsal  part,  forms  the  lining  of  a  spherical 
sac,  known  as  the  yolk-sac  (Fig.  25,  H).  In  birds  the  mass  of  yolk, 
which  may  be  regarded  as  lodged  in  the  thickened  ventral  wall  of  the 
yolk-sac,  is  so  extensive  that  the  cavity  of  the  sac  is  merely  a  flattened 
dorsal  cleft.  The  yolk-sac  gives  rise  to  the  entire  intestinal  tube,  together 
with  all  its  outgrowths.  They  are  therefore  lined  with  entoderm,  and 
they  develop  as -follows. 

At  first,  in  the  chick  embryo  (Figs.  27  and  28)  a  flattened  finger-like 
extension  of  the  yolk-sac  projects  forward  into  the  head,  under  the  noto- 
chor'd.  This  outpocketing  is  the  fore-gut,  which  gives  rise  to  the  pharynx, 
oesophagus,  stomach,  and  anterior  part  of  the  small  intestine.  Near  its 
anterior  extremity  it  comes  in  contact  with  the  entoderm  and  fuses  with 
At,  thus  forming  the  oral  membrane.  By  the  rupture  of  this  membrane, 
an  opening  from  the  exterior  into  the  pharynx  is  produced. 

Similarly  the  hind-gut  develops  as  a  pocket  from  the  posterior  part 
of  the  yolk-sac.  It  gives  rise  to  the  lower  portion  of  the  small  intestine 
and  the  entire  large  intestine,  and  fuses  with  the  ectoderm,  forming  the 
cloacal  membrane.  In  later  stages  the  ventral  part  of  the  posterior 
end  of  the  hind-gut  becomes  cut  off  from  the  dorsal  part;  the  ventral 
subdivision  forms  the  bladder,  and  the  dorsal  subdivision  becomes  the 
lowest  part  of  the  rectum.  At  the  same  time  the  cloacal  membrane  is 
correspondingly  subdivided  into  the  urogenital  membrane  which  closes 
the  outlet  of  the  bladder,  and  the  anal  membrane  which  closes  the  rectum. 
Later  these  membranes  rupture,  and  the  line  of  separation  between  ecto- 
derm and  entoderm  is  then  difficult  to  determine.  The  entoderm  ap- 
parently lines  the  entire  urethra  in  the  female,  but  only  the  upper  or  pro- 
static  portion  in  the  male;  the  remainder  is  lined  with  ectoderm. 

In  addition  to  forming  the  lining  of  the  pharynx  and  entire  digestive 
tube,  together  with  the  bladder  and  its  outlet,  the  entoderm  lines  the 
following  important  organs,  which  arise  as  outgrowths  of  the  pharynx  and 
digestive -tube :  the  auditory  tube,  extending  from  the  pharynx  to  the  ear; 
the  thyreoid  gland  and  certain  constituents  of  the  thymus;  the  entire 
respiratory  tract,  including  the  larynx,  trachea  and  lungs;  the  liver;  and 
the  pancreas. 

Mesoderm.  The  mesoderm  has  already  been  described  as  forming 
splanchnic  and  somatic  layers.  These  are  indicated  in  the  diagram  Fig. 
25,  H,  but  are  more  accurately  shown  in  Fig.  29,  which  corresponds  to 
the  upper  part  of  Fig.  25,  H,  under  higher  magnification.  Where  the 
somatic  and  splanchnic  layers  come  together  they  are  greatly  thickened, 
and  the  thickened  part  becomes  cut  into  block-like  masses  by  a  series 
of  transverse  clefts.  The  masses  are  called  mesodermic  somites,  and  a 
pair  of  them  occurs  in  each  transverse  segment  of  the  body.  They  in- 


4o 


HISTOLOGY 


crease  in  number  as  new  ones  become  cut  off  from  the  unsegmented 
mesoderm  in  the  posterior  part  of  the  embryo.     At  first  each  somite  may 


Med.  groove 


Prim,  knot 


Fig.  27.  Fig.  28. 

FIGS.  27  AND  28. — RECONSTRUCTIONS  OF  A  CHICK  EMBRYO,  INCUBATED  APPROXIMATELY  30  HOURS.  Xso. 

FIG.  27  represents  a  dorsal  view.  The  ectoderm  has  been  removed  except  around  the  rhomboidal  sinus 
and  under  the  head.  On  the  left  side,  all  the  mesoderm  except  the  blood  vessels  has  also  been  re- 
moved; a  portion  including  nine  somites  remains  on  the  right  side.  The  lowest  layer  beneath  the 
vessels,  is  the  entoderm.  Fig.  28  is  a  median  sagittal  section,  except  that  the  entire  heart  has  been 
included.  Ant.  neur.,  anterior  neuropore;  Med.  groove,  medullary  groove;  Med.  tube,  medullary 
tube;  Mes.  som.,  mesodermic  spmite;  Opt.  ves.,  optic  vesicle;  Oral  mem.,  oral  membrane;  Peric.  cav., 
pericardial  cavity;  Pr.  knot,  primitive  knot;  Pr.  str.,  primitive  streak;  R.  sinus,  rhomboidal  sinus; 
Vit.  v.,  vitelline  vein;  W.  duct,  Wolffian  duct. 

contain  a  cavity,  which  is  an  extension  of  the  ccelom,  but  the  cavity  is 
soon  obliterated  by  a  plug  of  cells.  In  dorsal  view  some  of  the  somites 
are  shown  on  the  right  side  of  Fig.  27;  the  rest  have  been  cut  away. 


GERM   LAYERS  41 

In  later  stages  each  somite  gives  rise  to  a  stream  of  cells  which  spread 
around  the  medullary  tube,  notochord  and  aorta.  After  these  cells  have 
been  given  off,  the  somite  appears  as  a  plate-like  structure  (Fig.  30), 
known  as  the  dermo-myotome.  The  principal  derivative  of  the  dermo- 
myotome  is  the  voluntary  musculature  of  the  body.  In  producing  the 
various  voluntary  or  skeletal  muscles,  certain  cells  of  the  dermo-myo- 
tome become  transformed  into  muscle  fibers.  These  are  at  first  arranged 
in  segmental  masses,  but  the  masses  become  subdivided  into  groups 
representing  the  individual  muscles.  The  groups  become  separated 
from  one  another  and  shift  to  their  final  positions.  Subsequently  they 


FIG.  29. 


FIG.  30. 


FIG.  29. — TRANSVERSE  SECTION  OF  A  RABBIT  EMBRYO  MEASURING  4.4  MM.     (9$  DAYS).    X6o. 
FIG.  30. — TRANSVERSE  SECTION  OF  A  RABBIT  EMBRYO    MEASURING   5  MM.     (n  DAYS).     X40. 
Ect.,    ectoderm;    -Ent.,    entpderrn;    Int.,    intestine;    Med.    tube,   medullary  tube;  Msnch.,  mesenchyma; 
Msth.,  mesodermal    epithelium;    Nch.,  notochord;  Som.,  somatopleure:  Som.  mes.,  somatic   meso- 
derm;  Spl.,  splanchnopleure ;  Spl.  mes.,  splanchnic  mesoderm;  W.  d.,  Wolffian  duct. 

acquire  their  connections  with  the  bones,  which  develop  later  than  the 
muscles.  The  remainder  of  the  dermo-myotome  breaks  up  into  cells 
which  are  contributed  to  the  deep  portion  of  the  skin. 

Connecting  the  somites  with  the  lateral  somatic  and  splanchnic 
layers  of  the  mesoderm,  there  is  a  narrow  neck  of  cells  (as  seen  in  cross 
section,  Fig.  29)  which  is  known  as  the  intermediate  cell  mass,  or 
nephrotome.  The  nephrotomes  at  first  are  not  segmentally  divided,  but 
form  the  floor  of  a  longitudinal  groove  in  the  mesoderm,  lateral  to  the 
somites  (Fig.  27).  The  nephrotomes  give  rise  dorsally  to  a  longitudinal 
cord  of  cells,  which  later  becomes  a  tube,  and  is  known  as  the  Wolffian 
duct  (Figs.  27,  29,  and  30).  It  lies  in  the  groove  above  the  nephrotomes. 
This  duct  grows  posteriorly  and  acquires  an  opening  into  the  entodermal 
bladder.  The  nephrotomes  then  become  separated  from  the  somites 
and  from  the  lateral  layers  of  the  mesoderm,  and  their  cells  become  ar- 
ranged so  as  to  form  coiled  tubes,  which  empty  into  the  Wolffian  duct. 
In  this  way  the  mesoderm  gives  rise  to  the  renal  system,  which  consists 
essentially  of  coiled  mesodermal  tubes,  receiving  urinary  products  from 


42  HISTOLOGY 

the  blood  and  conveying  them  through  the  Wolfnan  duct  to  the  bladder. 
Later,  parts  of  the  urinary  system  lose  their  primary  function  and  become 
the  ducts  of  the  genital  system. 

The  lateral  somatic  and  splanchnic  layers  of  the  mesoderm  produce 
the  lining  of  the  pleural,  pericardial,  and  peritoneal  subdivisions  of  the 
ccelom,  as  already  stated.  They  give  rise  also  to  an  important  tissue 
known  as  mesenchyma.  With  the  production  of  mesenchyma  the  tissues 


Epi. 


I.S. 


FIG.  31. — SECTION  FROM  THE  HEAD  OF  A  RABBIT  EMBRYO  OF  10$  DAYS,  4.4  MM.,  TO  SHOW  MESENCHYMA. 

Epi.  and  M.  T.,  Ectodermal  epithelium  of  the  epidermis  and  medullary  tube,  respectively.  N.,  nucleus, 
Pv  protoplasm,  and  I.  S.,  intercellular  substance  of  a  mesenchymal  cell.  Two  of  these  cells  show 
mitotic  figures.  B.  V.,  Blood  vessel,  lined  with  endothelium.  One  of  the  blood  vessels  contains  an 
embryonic  red  blood  corpuscle. 


of  the  embryo  may  be  divided  into  two  sorts,  namely,  epithelium  which 
covers  an  external  or  an  internal  surface  of  the  body,  and  mesenchyma 
which  fills  the  space  between  two  layers  of  epithelium.  These  relations 
are  clearly  shown  in  the  cross  section  of  the  abdomen  (Fig.  30).  The 
body  wall  consists  of  a  layer  of  ectodermal  epithelium  externally,  and  of 
mesodermal  epithelium  internally,  with  a  thick  layer  of  mesenchyma 
between  the  two.  Similarly  the  intestinal  wall  consists  of  mesodermal 
epithelium  toward  the  coelom,  and  entodermal  epithelium  toward  the 
intestine,  with  mesenchyma  between  them.  Epithelium  is  thus  pro- 
duced by  all  the  germ  layers,  but  mesenchyma  is  almost  exclusively  the 
product  of  the  mesoderm.  It  is  formed  not  only  from  the  lateral  splanchnic 


GERM   LAYERS  43 

and  somatic  layers  of  the  mesoderm,  but  also  from  the  somites.  The 
tissue  which  has  been  described  as  spreading  from  the  somites  around 
the  medullary  tube,  notochord  and  blood  vessels,  and  into  the  deep 
portion  of  the  skin,  is  mesenchyma.  It  also  surrounds  the  tubules  derived 
from  the  nephrotome. 

Under  higher  magnification,  as  in  Fig.  31,  it  is  seen  that  epithelium 
is  a  layer  of  closely  compacted  cells,  but  that  mesenchyma  is  a  proto- 
plasmic network,  the  meshes  of  which  are  filled  with  a  fluid  intercellular 
substance.  If  this  substance  is  abundant,  the  nuclei  of  the  mesenchyma 
are  widely  separated,  as  in  the  figure;  but  if  it  is  scanty  they  are  quite 
close  together.  Mesenchyma  gives  rise  to  a  great  variety  of  tissues, 
including  involuntary  muscle,  adipose  tissue,  cartilage,  and  bone.  Both 
the  cells  and  the  intercellular  substance  may  become  variously  modified. 
The  most  widespread  derivative  of  mesenchyma  is  connective  tissue, 
which  invests  the  nerves,  vessels,  muscles  and  epithelial  structures,  bind- 
ing them  together  in  organs,  and  filling  the  interstices  of  the  body. 


c 

FIG.  32. — WALL  OF  THE  YOLK-SAC  FROM  A  CHICK  OF  THE  SECOND  DAY  OF  INCUBATION.     (Minot.) 

Mes.,  Splanchnic  mesoderm;  Ent.,  entoderm,.  four  distinct  cells  of  which  are  shown  at  c;  V,  V,  blood 

vessels   containing  a  few  young  blood  cells. 


The  origin  of  the  blood  and  blood  vessels  remains  to  be  considered. 
In  very  early  stages  the  vessels  appear  as  cellular  strands,  some  of  which 
contain  a  lumen,  situated  between  the  mesoderm  and  entoderm.  Asso- 
ciated with  these  strands,  but  further  out  on  the  yolk-sac,  there  are 
clusters  or  "islands"  of  blood  cells,  surrounded  by  a  thin  layer  of  flattened 
cells  known  as  endothelium.  The  entire  system  soon  forms  a  network 
of  distinct  vessels  situated  in  the  splanchnopleure  (Figs.  29  and  32). 
The  formation  of  this  primary  vascular  network  in  rabbit  embryos  has 
been  described  by  Bremer  (Amer.  Journ.  of  Anat.,  1912,  vol.  13,  pp. 
111-128).  Generally  the  vessels  and  the  corpuscles  within  them  are 
considered  to  be  mesodermal,  but  some  authorities  have  regarded  them  as 
entodermal,  and  others  have  proposed  to  describe  them  as  forming  a 
separate  germ  layer  or  "angioblast"  (more  appropriately  angioderm). 

In  the  chick  embryo  shown  in  Figs.  27  and  28,  the  network  of  vessels 


44  HISTOLOGY 

in  the  splanchnopleure  has  formed  a  complete  circulatory  system.  By 
a  process  of  folding,  portions  of  the  net  have  been  brought  together 
under  the  fore-gut,  where  the  vessels  from  the  two  sides  have  fused  and 
formed  a  single  median  tube,  the  heart.  The  two  large  trunks,  derived 
from  the  network,  which  convey  the  blood  from  the  yolk-sac  to  the  heart 
are  known  as  vitelline  veins.  The  heart  divides  anteriorly  into  two 
vessels  (the  aorta)  which  pass  from  the  under  side  of  the  fore-gut  to  the 
upper  side,  and  then  extend  posteriorly.  They  finally  connect  by 
branches  with  the  network  over  the  yolk,  from  which  they  have  been 
derived.  Through  this  system,  nutriment  taken  from  the  yolk  is  brought 
to  the  heart  by  the  vitelline  veins,  and  distributed  throughout  the  body 
by  the  aortae. 

In  mammals  also,  a  complete  system  of  vessels  is  established  early 
in  development,  and  it  is  believed  that  all  later  vessels  arise  as  branches 
of  this  primary  endothelial  network.  If  this  opinion  is  correct,  none  of 
the  later  vessels  are  formed  by  the  coalescence  of  mesenchymal  spaces, 
or  by  transformation  of  mesenchymal  cells  into  endothelial  cells,  but 
only  as  outgrowths  of  pre-existing  endothelium.  There  is,  however, 
a  very  close  connection  between  the  endothelium  and  the  surrounding 
mesenchyma,  as  shown  in  Fig.  31. 

The  histogenesis  of  the  blood  is  likewise  very  difficult  to  follow.  The 
simplest  interpretation  is  one  which  has  not  been^disproven,  namely,  that 
all  forms  of  blood  corpuscles  are  descendants  of  the  cells  found  in  the 
blood  islands  of  the  yolk-sac.  According  to  this  hypothesis  these  cells 
multiply  in  certain  places  to  which  they  have  been  carried  by  the  circulating 
blood,  for  example  in  the  liver  in  later  embryonic  life  and  in  the  bone 
marrow  of  the  adult;  and  they  differentiate  into  the  red  and  white  corpus- 
cles of  various  kinds.  The  difficulties  which  this  hypothesis  encounters 
will  be  discussed  in  later  chapters. 

THE  FUNDAMENTAL  TISSUES. 

From  the  foregoing  outline  of  embryological  development,  it  is  clear 
that  all  the  organs  of  the  body  are  derived  from  a  relatively  small  number 
of  fundamental  tissues.  After  the  fertilized  egg  has  segmented,  it  gives 
rise  to  layers  of  cells,  of  which  the  ectoderm  and  entoderm  are  epithelial 
from  the  beginning.  The  mesoderm  very  early  divides  into  two  tissues — 
epithelium,  which  lines  the  body  cavity,  and  mesenchyma,  which  forms 
the  internal  substance  of  the  body  wall  and  intestinal  wall.  Thus  epithe- 
lium and  mesenchyma  may  be  regarded  as  the  primary  tissues  of  the  body. 
The  groups  of  blood  corpuscles,  which  are  probably  derived  from  the 
mesenchyma,  and  the  endothelium  which  surrounds  them,  also  arise 
very  early,  and  these  may  be  set  apart  as  vascular  tissue. 


GERM   LAYERS  45 

The  nervous  system  develops  from  epithelium,  but  its  cells,  singly 
or  in  groups,  become  imbedded  in  strands  and  masses  of  nerve  fibers  which 
these  same  cells  send  out  as  processes.  Thus  little  remains  in  the  adult 
to  suggest  that  the  brain  or  peripheral  nerves  come  from  a  layer  of  cells 
covering  a  surface,  and  the  nervous  system  is  therefore  described  as  con- 
sisting of  nervous  tissue. 

The  voluntary  muscles  are  formed  from  cells  derived  from  the  epithe- 
lium of  the  mesodermic  somites,  but  they  develop  as  the  somite  breaks 
up  and  its  epithelial  character  is  lost.  The  involuntary  muscles  are  pro- 
duced by  a  transformation  of  mesenchymal  cells  into  elongated  muscle 
cells.  For  physiological  reasons  these  two  kinds  of  muscle,  which  are 
of  diverse  origin  and  structure,  are  classed  together  as  muscular  tissue. 

The  relation  of  the  germ  layers  to  the  five  fundamental  tissues  which 
have  now  been  recognized,  is  shown  in  the  following  summary. 

ORIGIN  OF  THE  TISSUES  FROM  THE  GERM  LAYERS. 

The  ectoderm  produces: 

1 .  EPITHELIUM  of  the  following  organs : — the  skin  (epidermis)  including  the  cutane- 
ous glands,  hair  and  nails;  the  cornea  and  the  lens;  the  external  and  internal  ear;  the 
nasal  and  oral  cavities,  including  the  salivary  glands,  the  enamel  of  the  teeth  and  ante- 
rior lobe  of  the  hypophysis;  the  anus;  the  cavernous  and  membranous  parts  of  the  male 
urethra;  together  with  that  epithelium  of  the  chorion  which  is  toward  the  uterus  and 
of  the  amnion  which  is  toward  the  embryo. 

2.  NERVOUS  TISSUE  forming  the  entire  nervous  system,  central,  peripheral  and 
sympathetic. 

3.  MUSCULAR  TISSUE,  rarely,  as  of  the  sweat  glands,  and  iris. 
The  mesoderm  produces: 

1.  EPITHELIUM  of  the  following  four  sorts:  (i)  epithelium  of  the  urogenital  organs 
(except  most  of  the  bladder  and  the  urethra)  and  the  epithelioid  cords  of  cells  in  the 
suprarenal  gland;  (2)epithelium  of  the  pericardium,  pleurae,  and  peritoneum  and  the 
continuation  of  this  layer  over  the  contiguous  surfaces  of  amnion  and  chorion;  (3)  epi- 
thelium lining  the  blood  vessels  and  lymphatic  vessels;  and  (4)  epithelium  lining  the 
joint  cavities  and  bursae. 

2.  MUSCULAR  TISSUE,  striated  (voluntary),  cardiac,  and  smooth  (involuntary). 

3.  MESENCHYMA,  an  embryonic  tissue,  which  forms  in  the  adult,  connective  and 
adipose  tissue,  bone  (including  the  teeth  except  their  enamel),  cartilage,  tendon,  and 
various  special  cells. 

4.  VASCULAR  TISSUE,  the  cells  of  the  blood  and  lymph,  consequently  the  essential 
elements  of  the  lymph  glands,  red  bone  marrow  and  spleen. 

The  entoderm  produces: 

1.  EPITHELIUM  of  the  following  organs: — the  pharynx,  including  the  auditory 
tube  and  middle  ear,  thyreoid  and  thymus  glands;  the  respiratory  tract,  including 
larynx,  trachea,  and  lungs;  the  digestive  tract,  including  the  oesophagus,  stomach, 
small  and  large  intestine,  rectum,  liver,  pancreas,  and  the  yolk-sac;  and  part  of  the 
urinary  organs,  namely  most  of  the  bladder,  the  female  urethra,  and  prostatic  part 
of  the  male  urethra  (including  the  prostate). 

2.  NOTOCHORDAL  TISSUE,  which  occurs  in  the  nuclei  pulposi. 


46  HISTOLOGY 

In  the  following  pages  the  fundamental  tissues  will  be  considered  in 
turn.  In  connection  with  them,  certain  organs  will  be  examined.  An 
organ  is  a  more  or  less  independent  portion  of  the  body,  having  a  connect- 
ive tissue  framework,  and  a  special  blood,  lymph,  and  nerve  supply, 
in  addition  to  its  characteristic  essential  cells.  The  essential  cellular 
substance  of  an  organ,  in  distinction  from  the  accessory  tissues,  is  often 
called  its  parenchyma;  the  accessory  supporting  tissues  constitute  the 
stroma  (Gr.  <rr/o<o/«x,  bed),  in  which  the  parenchyma  is  imbedded. 

Such  structures  as  the  pancreas  and  liver  are  obviously  organs.  An 
individual  muscle  or  a  particular  bone,  which  has  a  connective  tissue 
covering  or  framework,  and  a  supply  of  vessels  and  nerves,  besides  its 
essential  substance,  may  also  be  regarded  as  an  organ.  The  organs  which 
are  of  widespread  occurrence,  such  as  the  bones,  muscles,  tendons  and 
large  vessels,  will  be  described  with  the  tissues.  The  more  complex 
organs  are  reserved  for  a  later  section,  entitled  "Special  Histology." 

EPITHELIUM. 

The  Dutch  anatomist,  Frederik  Ruyseh,  recognized  that  the  covering 
of  the  margin  of  the  lips  is  not  identical  with  the  epidermis.  "There- 
fore," he  wrote,  "I  shall  call  that  covering  the  epithelis,  or  papillary  in- 
tegument of  the  lips"  (Thesaurus  anat.  Ill,  1703,  No.  23,  p.  26).  It  is 
an  unfortunate  name  (cut,  upon  OrjXrj,  Latin  papilla,  the  nipple)  since  it 
does  not  refer  to  the  layer  upon  the  nipple,  but  to  that  which  covers  a 
great  number  of  nipple-like  elevations  of  the  underlying  tissue.  Such 
elevations  or  papilla  are  indeed  abundant  in  the  lips,  but  they  occur  also 
under  the  epidermis.  Ruyseh  substituted  epithelia  for  epithelis  in  other 
sections  of  his  work,  and  Haller,  writing  some  years  later,  used  the  neuter 
epithelium,  so  that  epithelia  thus  became  a  plural. 

As  the  term  epithelium  is  now  used,  it  includes  the  epidermis,  and  the 
lining  of  the  various  internal  tubes  and  cavities.  It  has  been  denned  as 
a  layer  of  closely  compacted  cells,  covering  an  external  or  internal  surface 
of  the  body,  having  one  of  its  surfaces  therefore  free,  and  the  other  rest- 
ing on  underlying  tissue.  But  the  term  is  also  correctly  applied  to  solid 
outgrowths  from  such  layers,  either  in  the  form  of  cords  or  masses'  of 
cells.  Usually  these  outgrowths  subsequently  acquire  a  cavity,  or  lumen, 
around  which  the  cells  become  arranged  in  a  layer. 

The  epithelia  which  cover  the  skin  and  line  the  digestive  tube  and 
urogenital  organs  are  thick,  as  compared  with  those  which  line  the  body- 
cavity,  the  vessels,  and  the  synovial  cavities.  For  these  thin  layers  His 
(1865)  introduced  the  term  endothelium.  He  wrote  as  follows: 

We  are  accustomed  to  designate  the  layers  of  cells  which  cover  the  serous  and 
vascular  cavities  as  epithelia.  But  all  the  layers  of  cells  which  line  the  cavities  within 


EPITHELIUM 


47 


M 


the  middle  germ  layer  have  so  much  in  common,  and  from  the  time  of  their  first  ap- 
pearance differ  so  materially  from  those  derived  from  the  two  peripheral  germ  layers, 
that  it  would  be  well  to  distinguish  them  by  a  special  term — either  to  contrast  them,  as 
false  epithelia,  with  the  true,  or  to  name  them  endothelia,  thus  expressing  their  relation 
to  the  inner  surfaces  of  the  body. 

The  name  endothelium,  etymologically  absurd,  has  become  generally 
accepted  for  the  lining  of  the  blood  vessels  and  lymphatic  vessels.  For 
the  other  forms  of  epithelium  which  it  was  intended  to  include,  special 
names  have  been  proposed. 

Minot  (1890)  introduced  mesothelium  to  designate  the  layer  of  meso- 
dermal  cells  which  bounds  the  body  cavity.  Thus  mesothelium  does  not 
include  the  endothelium  of  the  vessels,  or  the  lining  of  the  synovial  cavi- 
ties; but  it  does  include  the  cells  of  the  nephrotome,  through  which  the 
body  cavity  may  extend,  and  also  the  epithelium  which  bounds  the  somites 
in  early  stages.  Professor  Minot  applies  the  term  also  to  the  thick  epithe- 
lium of  the  renal  organs,  which  is  derived  from  the  cells  of  the  nephrotome. 

As  seen  in  Fig.  33,  the  epithelium  lining  the  vessels  closely  resembles 
that  which  lines  the  body  cavities,  and  to  a  certain  extent  this  justifies 
the  use  of  the  term  endothelium  for 
both  layers  as  proposed  by  His.  But 
it  has  been  shown  embryologically 
that  the  vessels  and  body  cavity  are 
of  different  origin,  and  are  distinct 
even  in  the  earliest  stages.  More- 
over the  linings  of  the  synovial  cavi- 
ties, tendon  sheaths,  and  the  chambers 
of  the  eye  form  a  third  separate  group. 
They  arise  relatively  late  in  develop- 
ment by  the  confluence  of  intercel- 
lular spaces  in  the  mesenchyma,  and 
they  are  therefore  bounded  by  flattened  mesenchymal  cells. 

In  accordance  with  these  embryological  facts,  the  following  use  of 
terms  is  here  proposed: 

Endothelium  should  be  restricted  to  the  lining  of  the  blood  vessels 
and  lymphatic  vessels. 

Mesothelium,  except  in  young  embryos,  should  be  restricted  to__the 
lining  of  the  body  cavity  and  its  subdivisions. 

Mesenchymal  epithelium  (or  false  epithelium)  should  be  applied  to 
the  lining  of  joint  cavities  and  bursae. 

All  of  these  forms  of  epithelium  are  primarily  thin  and  are  derived 
from  the  mesoderm.  The  lining  of  the  body  cavity  is,  however,  thickened 
in  places.  Thick  epithelium  may  be  ectodermal,  entodermal  or  meso- 
dermal  in  origin. 


•J?  X 


•,•• 

X 


T 
•>  ^ 


FIG.  33. 

A,  Surface  view  of  mesothelium  from  the  mesen- 
tery; B,  surface  view  of  endothelium  from  an 
artery. 


48  HISTOLOGY 

Epithelia  differ  from  one  another,  not  only  in  origin,  but  also  in  the 
shape  of  their  cells,  the  number  of  layers  of  which  they  are  composed,  and 
the  differentiation  of  their  cells.  These  features  should  be  examined  in 
every  specimen  studied,  and  something  under  each  heading  should  be 
recorded  in  any  complete  description  of  an  epithelium. 

SHAPES  OF  EPITHELIAL  CELLS  AND  THE  NUMBER  OF  LAYERS. 

An  epithelium  which  consists  of  but  one  layer  of  cells  is  called  a  simple 
epithelium,  and  its  cells  may  be  flat,  cuboidal  or  columnar.  These  terms 
refer  to  the  appearance  of  the  cells  when  cut  in  a  plane  perpendicular  to 
the  free  surface.  If  in  such  a  section  the  outlines  of  the  cells  are  approxi- 
mately square,  as  along  the  upper  surface  in  Fig.  34,  the  epithelium  is 
cuboidal;  if  they  are  stretched  out  in  a  thin  layer  so  that  they  appear 
linear,  as  along  the  lower  surface  in  Fig.  34,  the  epithelium  is  flat.  Endo- 
thelium  is  an  extremely  flat  epithelium,  in  which  the  cells  are  so  thin  that 
the  nuclei  cause  local  bulgings  of  the  cell  membrane.  If  the  epithelial 
cells  are  laterally  compressed,  so  that  tall  forms  result  as  in  Fig.  35,  B, 
the  epithelium  is  columnar.  Such  epithelium  is  less  accurately  called 

Cuboidal  epithelium. 
;.~"   Connective  tissue. 

Flat  epithelium. 

PIG.  34. — PORTION  OF  THE  MEMBRANES  SURROUNDING  A  PIG  EMBRYO  MEASURING  60  MM.     (Allantois 

above,  and  amnion  below.) 

cylindrical,  and  both  cuboidal  and  flat  epithelia  are  sometimes  referred 
to  as  pavement  epithelium.  Intermediate  forms,  which  are  described 
as  low  columnar  or  low  cuboidal,  frequently  occur.  The  cells  of  certain 
epithelia  change  their  shape  temporarily,  as  in  the  bladder  during  disten- 
tion,  in  the  oesophagus  during  deglutition,  and,  to  some  extent,  in  the 
arteries  with  every  pulsation.  During  post-mortem  contraction  the 
arterial  endothelium  is  considerably  thickened.  Moreover  during  embry- 
onic development,  epithelial  cells  may  change  from  one  form  to  another. 

On  surface  view  the  epithelial  cells  of  all  types  are  polygonal  and  usually 
six-sided  (Figs.  33  and  35,  A).  Geometrically  a  circle  would  come  in 
contact  with  six  surrounding  circles  of  equal  diameter,  and  a  cell  is  usually 
in  contact  with  six  surrounding  cells.  The  cells,  however,  vary  in  di- 
ameter, and  are  often  surrounded  by  five  or  seven  cells  and  occasionally 
by  four  or  eight. 

An  epithelium  which  consists  of  several  superimposed  layers  is  known 
as  stratified  epithelium  (Fig.  37).  In  such  cases  the  basal  cells  are  usually 


EPITHELIUM 


49 


columnar  and  closely  crowded.  They  multiply  by  mitosis  and  give  rise 
to  cells  which  are  pushed  toward  the  free  surface.  After  leaving  the  basal 
layer  they  enlarge  and  become  polygonal  in  outline.  "Toward  the  free 
surface  they  become  gradually  flattened,  and  may  be  more  or  less  cornified 
or  transformed  into  ty)rny  material.  These  scale-like  cells  are  called 


Cut. 


FIG.  35. — SIMPLE  COLUMNAR  EPITHELIUM 
FROM  A  HUMAN  INTESTINAL  VILLUS. 

A,  Surface  view;  B,  vertical  section.  The 
prominent  cell  outlines  in  A  are  due  to 
terminal  bars,  shown  in  section  in  B. 
Cut.,  cuticular  border. 


FIG.  36.— DETACHED  SQUA- 
MOUS CELLS  FROM  THE 
MOUTH. 


FIG.  37. — STRATIFIED   EPITHE- 
LIUM FROM  THE  (ESOPHAGUS 

OF  A  CHILD. 


squamous  cells  and  they  readily  become  detached  (Fig.  36).  Stratified 
epithelium  is  found  in  the  vagina,  oesophagus,  pharynx  and  oral  cavity; 
and  in  its  most  complex  form,  with  many  layers,  some  of  which  are  pecu- 
liarly modified,  it  constitutes  the  epidermis. 


- Columnar  cells 


Fusiform    cells' 

Basal  cells- 

Conn,    tisues. 


FIG.  38. 

FIG.  39. 

FlGS.  38  AND  39- — PSEUDO-STRATIFIED   CILIATED  EPITHELIUM  FROM  THE  HUMAN  RESPIRATORY  TRACT. 
Fig.  39  is  a  diagram  of  the  condition  shown  in  Fig.  38.   X72O. 

In  certain  organs  and  especially  in  embryos,  simpler  forms  of  stratified 
epithelium  occur,  which  are  described  as  four-layered,  or  two-layered  as 
the  case  may  be.  The  superficial  cells  may  be  flat,  cuboidal,  or  columnar. 
A  characteristic  epithelium  with  dome-shaped  outer  cells  and  tall  basal 
cells,  found  in  the  bladder  and  ureter,  is  known  as  "  transitional  epithe- 


50  HISTOLOGY 

lium,"  as  if  it  were  intermediate  between  the  simple  and  stratified  forms. 
When  the  bladder  contracts  the  cells  are  heaped  up  in  several  layers,  but 
when  distended  the  number  may  be  reduced  even  to  two. 

If  the  cell  walls  are  indistinct  and  the  sections  are  thick  or  oblique, 
the  number  of  layers  in  an  epithelium  may  be  very  difficult  to  determine. 
Thus  in  a  simple  epithelium  the  nuclei  may  be  at  different  levels  (Fig. 
35,  B),  and  if  the  section  is  not  vertical  it  will  show  several  layers,  ap- 
proaching the  condition  of  the  tangential  section,  Fig.  35,  A.  Fig.  38 
represents  a  vertical  section  of  an  epithelium  with  nuclei  at  three  levels, 
and  in  two  forms  (the  basal  nuclei  being  round  and  the  others  elongated) ; 
but  yet,  as  interpreted  in  Fig.  39,  it  is  not  stratified.  It  is  of  the  form 
known  as  pseudo-sir  atifted,,  in  which  all  the  cells  reach  the  underlying 
connective  tissue,  but  only  a  limited  number  extend  to  the  free  surface. 
Pseudo-stratified  epithelium  occurs  in  the  upper  part  of  the  respiratory 
tract,  including  the  trachea  and  larger  bronchi,  and  in  the  epididymis. 

PERIPHERAL  DIFFERENTIATION  OF  EPITHELIAL  CELLS. 

Free  surface.  The  free  surface  of  epithelial  cells  is  often  provided 
with  a  thickened  top-plate  or  cuticula.  Under  high  magnification  the 
cuticular  border  of  the  columnar  cells  in  the  intestine  is  seen  to  be  vertically 
striated  (Fig.  35,  B),  and  these  striations  have  been  interpreted  as  minute 
canals  through  which  protoplasmic  processes  may  be  sent  out  beyond 
the  free  surface.  In  some  cases,  however,  the  striated  cuticula  appears 
to  consist  merely  of  short,  parallel  protoplasmic  rods.  In  certain  cells 
of  the  kidney,  the  rods  may  become  somewhat  divergent,  giving  rise  to 
what  is  known  as  the  "brush  border."  Longer  processes,  which  are 
vibratile  but  not  retractile,  are  called  cilia  (the  Latin  term  for  eye- 
lashes). They  project  from  the  free  surface  of  certain  epithelial  cells 
in  the  trachea  and  bronchi  (Figs.  38  and  39),  in  the  uterus  and  uterine 
tube,  in  the  efferent  ducjjjtof  the  testis,  and  in  the  nasal  part  of  the  pharynx 
together  with  trfe  auditory  tube  and  naso-lachrymal  duct  which  open 
into  it.  In  the  living  condition  the  moti6n  of  cilia  may  be  observed  in 
various  unicellular  animals.  It  may  be  studied  advantageously  in 
fragments  from  the  margin  of  the  gills  of.  a  clam,  or  in  epithelium  from 
the  roof  of  the  mouth  of  a  frog.  The  cilia  are  numerous,  and  in  the  snail 
Heidenhain  counted  no  arising  from  a  single  cell.  They  do  not  act 
together,  but  rapidly  succeeding  waves,  due  to  the  bending  of  the  cilia, 
pass  over  the  entire  surface.  By  bending  -sharply  downward,  each 
cilium  creates  a  forward  current  in  the  overlying  fluid,  and  passes  the 
particles  above  it  to  the  cilium  in  front.  No  sooner  does  a  cilium  begin 
to  bend  than  the  next  in  front  takes  up  the  movement  and  thus  the  ciliary 
waves  are  propagated.  In  some  animals,  however,  the  wave  proceeds 


EPITHELIUM  51 

in  a  direction  opposite  to  that  of  the  effective  stroke.  Tke  cilia  in  man 
produce  currents  toward  the  outlets  of  the  body.  In  the  uterine  tube 
the  stroke  is  toward  the  uterus,  presumably  favoring  the  passage  of  the 
ova,  but  the  spermatozoa  ascend  this  tube  against  the  current. 

The  structure  of  cilia,  because  of  their  small  size,  is  difficult  to  deter- 
mine, but  in  many  cases  a  differentiation  between  the  exoplasm  and 
endoplasm  has  been  observed.  The  simplest  cilia,  as  shown  in  the 
diagram  (Fig.  40,  a),  are  essentially  permanent  pseudopodia,  with  con- 
tractile sheaths  and  fluid  contents.  They  may  develop  very  rapidly 
in  the  protozoa.  Thus  Prowazek  has  seen  processes  grow  out  in  eight 
minutes,  which  were  then  vibrating  19  .times  in  20  seconds.  Schafer 


..::;.;:W 

• 


FIG.  40. 

b,  c,   Diagrams  to  illustrate  the  structure 
of  cilia.     (After  Williams.) 


FIG.  41. 

a,  Diagram  of  a  ciliated  cell  (after  Prenant) , 
showing  yibratile  cilia;  b,  cells  of  the 
human  epididymis  (after  Fuchs),  showing 
non-motile  cilia. 


considers  that  cilia  are  primarily  pseudopodia,  and  that  their  motion 
is  caused  by  the  alternating  ingress  and  egress  of  fluid  to  and  from  the 
central  part,  due  to  variations  in  the  surface  tension. 

Many  cilia,  however,  appear  to  contain  more  or  less  solid  axial  rods, 
which  generally  proceed  from  round  basal  bodies  resembling  centrosomes. 
That  these  bodies  arise  from  the  centrosome  has  recently  been  denied. 
Sometimes  the  bodies  are  double,  and"  extensions  from  them  downward 
into  the  cytoplasm  may  occasionally  be  observed  (Fig.  41,  a).  These 
roots  approach  one  another  beside  the  nucleus,  and  it  has  been  discussed 
whether  or  not  they  unite.  The  roots,  and  portions  of  the  cytoplasmic 
reticulum  at  right  angles  to  the  shafts  of  the  cilia,  have  been  thought 
to  act  as  levers.  Others  conjecture  that  the  central  shaft  is  a  supporting 
structure,  perhaps  elastic,  which  is  surrounded  by  a  contractile  sheath. 
The  contractile  elements  may  extend  the  whole  length  of  the  cilium  or  be 
confined  to  its  base,  as  indicated  in  the  diagram  (Fig.  40,  b  and  c).  If 


HISTOLOGY 


the  sheath  were  equally  developed  about  the  entire  circumference  of  the 
axis,  the  cilia  should  be  able  to  strike  in  any  direction.  Usually  the 
effective  stroke  is  in  one  direction  only,  but  in  some  cases  it  may  be 
reversed.  In  reversible  cilia,  such  as  occur  on  the  labia  of  the  sea  anemone, 
the  effective  stroke  is  either  toward  the  mouth  or  away  from  it,  according 
to  the  chemical  composition  of  the  substances  in  contact  with  the 
cilia  (Parker,  Amer.  Journ.  of  Physiol.,  1905,  vol.  3,  pp.  1-16). 
In  such  a  case  the  contractile  material  is  supposed  to  be  gathered  in  two 
bands,  on  opposite  sides  of  each  cilium.  In  the  irreversible  cilia,  such  as 
are  found  elsewhere  in  the  sea  anemone  and  in  man,  the  contractile 
material,  according  to  Parker,  must  be  gathered  especially  on  one  side 
of  the  supporting  axis. 

The  whip-like  processes,  or  flagella,  which  form  the  tails  of  sperma- 
tozoa, may  be  compared  with  single  cilia.  Each  springs  from  a  body 
resembling  a  centrosome,  and  consists  of  an  axial  filament  with  a  sur- 
rounding sheath,  but  whether  the  filament  or  the  sheath  contains  the 
contractile  substance  is  still  uncertain. 

Non-motile  projections,  somewhat  resembling  cilia,  are  found  in  the 
cells  of  the  epididymis  (Fig.  41,  b).  They  have  no  basal  bodies,  and 
lack  the  distinctness  of  true  cilia.  Generally  they  appear  in  conical 
clumps,  which  have  been  compared  to  the  hairs  of  a  wet  paint  brush. 
They  may  be  concerned  with  the  discharge  of  secretion.  Other  non- 
motile  processes  of  epithelial  cells  are 
the  tapering  projections  of  the  sen- 
sory cells,  apparently  designed  to  re- 
ceive stimuli.  The  lining  of  the 
central  cavity  of  the  spinal  cord  and 
ventricles  of  the  brain  is  also  pro- 
vided with  short  projections,  which 
may  .be  degenerating  cilia.  It  is 
questionable  whether  these  are 
motile. 

Lateral  surface.  The  lateral  sur- 
faces of  epithelial  cells  may  be  in 
close  contact  with  one  another, 
sometimes  without  intervening  cell 
walls;  or  they  may  be  separated  by 
a  thin  layer  -  of  intercellular  substance,  which  is  generally  fluid.  Im- 
mediately beneath  the  cuticular  border  of  the  cells  lining  the  intestine, 
the  intercellular  substance  takes  the  form  of  a  more  solid  bar  encir- 
cling each  cell  and  binding  it  to  those  which  surround  it.  The 
arrangement  of  these  terminal  bars  is  shown  in  the  diagram,  Fig.  42, 
and  in  the  section  Fig.  35,  b.  If  the  section  passes  down  through  the 


Network  of  -, 
.  terminal  x\ 
bars. 


Cuticula. 


PIG.  42. — DIAGRAM  OF  THE  NETWORK  OF  TERMI- 
NAL BARS. 
The  two  cells  on  the  left  are  divided  lengthwise 

into  halves;  the  two  on  the  right  are  drawn 

as  complete  cylinders  or  prisms. 


EPITHELIUM  53 

middle  of  the  cell,  as  on  the  left  of  Fig.  35,  b,  the  bars  are  cut  across  and 
appear  as  points;  but  if  either  the  proximal  or  distal  side  of  the  cell  is 
included  in  the  section,  they  appear  as  lines,  as  on  the  right  of  the  figure. 
Terminal  bars  have  been  found  in  many  epithelia,  especially  in  mucous 
membranes  and  glands.  They  occur  in  the  epididymis  (Fig.  41,  b)  where 
they  appear  as  thickenings  of  the  cell  wall.  According  to  Stohr  they  are 
found  in  the  stratified  epithelium  of  the  tongue  and  bladder. 

The  intercellular  substance  in  endothelium  and  mesothelium  is  ordi- 
narily inconspicuous,  but  it  may  be  demonstrated  by  treating  the  tissue 
with  a  solution  of  silver  nitrate.  The  resulting  precipitate  occurs  chiefly 
in  the  intercellular  "cement  substance,"  which  then  appears  as  a  wavy 
black  line  bounding  each  cell  (Fig.  33).  It  is  of  importance  since  various 
forms  of  blood  corpuscles  make  their  way  through  it  from  the  vessels  into 
the  surrounding  tissue. 

In  the  lower  layers  of  the  epidermis  and  the  thick  oral  epithelium, 
the  intercellular  substance  is  clearly  seen,  and  here  it  is  bridged  by  spiny 
processes   from    the   adjacent    cells.      These   inter- 
cellular   bridges    occur   in   endothelium   and   many 
forms   of   epithelium,    but   they   are  most  readily 
observed  in  the  deep  layers  of  the  thick  stratified 
epithelia  (Fig.  43).     Within  the  bridges,  fibrils  pass 
from  cell  to  cell.     In  the  intercellular  spaces  between 
the  spiny  processes,  nutrient  fluid  makes  its  way  to     FlG<  ^^3!  AS° SEENL  m 
the  outer  layers.     Whatever  nutriment  they  receive          Sfm^wulS^™ 
must   be    derived    from    the  intercellular  fluid   or          DERM?S.°F 
through   the  bodies  of  the   underlying  cells,  since 
neither  blood  vessels  nor  lymphatic  vessels  penetrate  the  epithelium. 
This  is  probably  true  of  all  epithelia  in  man,  but  in  the  bladder  and  renal 
pelvis  the  blood  vessels  approach  very  close  and  may  appear  to  enter, 
and  in  the  amphibia,  according  to  Maurer,  capillaries  may  be  observed 
well  within  the  oral  epithelium.     Nerve  fibers  extend  among  the  basal 
cells  of  the  epidermis  and  other  e'pithelia,  and  ramify  in  contact  with 
these  cells,  but  special  methods  are  required  to  demonstrate  them. 

Basal  surface.  The  basal  cells  of  an  epithelium  sometimes  seem  to 
send  out  processes  which  blend  with  the  underlying  connective  tissue. 
Usually,  however,  the  lower  surface  is  well  defined,  and  the  epithelium 
is  bound  down  by  intercellular  cement  substance.  Often,  especially  in 
glands,  the  epithelium  rests  upon  a  thin,  well-defined  basement  membrane 
or  membrana  propria.  This  membrane  is  usually  homogeneous  and  con- 
tains very  few  nuclei.  Sometimes  it  is  composed  of  elastic  tissue.  Certain 
basement  membranes  have  been  considered  as  derivatives  of  the  epithe- 
lium, but  generally  they  are  clearly  of  mesenchymal  origin. 


54 


HISTOLOGY 


PROCESSES  OF  SECRETION  IN  EPITHELIAL  CELLS. 

Many  epithelial  cells  elaborate  and  discharge  substances  which  do 
not  become  parts  of  the  tissue.  Such  cells  are  called  gland  cells,  and  their 
products  are  either  utilized  by  the  body  (secretions)  or  eliminated  as  waste 
products  (excretions).  The  process  of  elaboration  and  discharge  of  the 
secretion  or  excretion  may  often  be  recognized  by  changes  in  the  form 
and  contents  of  the  cell.  A  gland  cell  which  is  full  of  secretion,  or  dis- 
charging it,  is  called  "active,"  and  one  in  which  the  secretion  is  not 
apparent,  though  it  may  be  in  process  of  formation,  is  called  "resting." 
The  appearances  during  secretion  differ  in  two  types  of  gland  cells — the 
serous,  which  produce  watery  secretions,  like  saliva;  and  the  mucous, 
which  form  thick  secretions,  like  those  of  the  nose  and  throat.  These 
will  be  considered  in  turn. 

Serous  gland  cells,  when  empty,  are  small  and  darkly  staining.    As 


Granule. 


Protoplasm. 


Basal  filaments. 


Granule. 


Protoplasm. 


New  granule. 


Nucleus.  X^diRJP 

'Large  nucleolus. 
A  B 

PIG.  44. — Two  SEROUS  GLAND-CELLS  FROM  THE  SUBMAXILLARY  GLAND  OF  A  GUINEA-PIG.  X  1260. 
In  cell  B  the  granules  have  passed  into  the  unstainable  state;  new  stainable  granules  are  beginning  to 

develop  in  the  protoplasm. 

the  formation  of  secretion  begins,  the  cells,  if  prepared  with  special 
methods,  exhibit  granules  which  stain  intensely.  These  granules  have 
become  cut  off  from  the  basal  filaments  or  mitochondria  (Fig.  44,  A). 
They  enlarge,  lose  their  staining  capacity,  and  are  transformed  into  drops 
of  secretion.  The  entire  cell  becomes  larger  and  clearer  than  before,  and 
the  alveolar  structure  of  its  protoplasm  is  well  marked  (Fig.  44,  B). 
Finally  the  droplets  become  confluent  and  are  discharged  from  the  free 
surface  of  the  cell.  A  portion  of  the  mitochondria  remains  behind  as 
the  source  of  further  secretion.  In  many  gland  cells  the  cytoplasmic 
differentiation  is  accompanied  by  changes  in  the  nucleus.  In  the  empty 
cell  the  nucleus  has  distinct  nucleoli  and  a  fine  chromatic  reticulum,  but 
in  cells  full  of  secretion  the  nucleoli  have  enlarged  or  disappeared  and  the 
chromatin  is  in  the  form  of  coarse  masses.  Particles  pass  from  the  nucleus 
into  the  cytoplasm,  and  these  have  been  said  to  give  rise  to  secretory 
granules. 

In  mucous  cells  the  process  of  secretion  also  begins  with  granule  for- 
mation, but  the  mucigen  granules  gather  near  the  free  surface  of  the  cell 


GLANDS 


55 


FIG.  45. — EPITHELIAL  CELLS  SECRETING  Mucus. 
From  a  section  of  the  mucous  membrane  of  the  human  stomach 
Xs6o.  p,  Protoplasm;  s,  secretion;  a,  three  cells,  two  empty, 
the  third  showing  the  beginning  of  mucoid  metamorphosis;  e,  the 
cell  on  the  right  is  discharging  its  contents;  the  granular  proto- 
plasm has  increased  and  the  nucleus  has  become  round  again. 


where  they  become  changed  into  clear  droplets  of  mucus.  A  discoid 
mass  of  secretion  is  thus  produced  which  is  quite  sharply  marked  off  from 
the  underlying  cytoplasm 
(Fig.  45,  a  and  b).  As  *-  „ 
the  cytoplasm  becomes 
increasingly  transformed 
into  secretion,  the  elon- 
gated nucleus  becomes  at 
first  round,  and  then  flat- 
tened. It  is  forced  to 
the  base  of  the  cell  where 
it  is  lodged  in  a  small  amount  of  unchanged  cytoplasm  (Fig.  45,  b-d). 
The  secretion  is  then  gradually  discharged  through  the  distended  top- 
plate,  which  is  often  ruptured  in  sections,  and  the  nucleus  again  becomes 

round  and  moves  toward  the  cen- 
ter of  the  cell.  Most  gland  cells 
are  not  destroyed  by  the  act  of 
secretion,  but  may  repeat  the 
process  several  times.  An  ex- 
ception occurs  in  the  case  of  the 
sebaceous  glands,  in  which  the 
cells  disintegrate  and  are  cast  off 
with  their  products.  In  the 
mucous  cells  of  the  intestine, 
secretion  is  formed  below  and 
discharged  from  the  free  surface 
at  the  same  time.  The  cells,  as 
seen  in  Fig.  46,  arise  near  the 
bottom  of  tubular  depressions 
lined  with  simple  columnar  epi- 
thelium. By  the  formation  of 
new  cells  below  them  they  are 
pushed  toward  the  outlet  of  the 
tube.  Thus  the  youngest  cells 
are  at  the  bottom  of  the  pit  and 
the  oldest  are  at  the  top.  For  a 
time  the  secretion  develops  faster 
than  it  is  discharged,  and  the 
cells  enlarge  as  seen  in  the  middle 
part  of  the  gland;  later,  as  elimi- 
nation exceeds  production,  they 
become  narrow,  and  their  final 
stages,  as  compressed  cells  with 


Secretion. 

Protoplasm 
and  nucleus. 


Gland  lumen. 


FIG.  46.— INTESTINAL  GLAND  FROM  A  SECTION  OF  THE 

HUMAN  LARGE  INTESTINE.  X  165. 
The  secretion  formed  in  the  goblet-cells  is  here  col- 
ored blue;  usually  it  is  pale  as  in  Fig.  45.  In  zone  I 
the  goblet-cells  show  the  beginning  of  secretion;  that 
expulsion  has  begun  is  evident  from  the  presence  of 
drops  of  secretion  in  the  lumen  of  the  gland.  2, 
Goblet-cells  with  much  secretion.  3,  Goblet-cells 
containing  less  secretion.  4,  Dying  goblet-cells, 
some  of  which  still  contain  remnants  of  secretion. 


56  HISTOLOGY 

a  remnant  of  secretion,  are  found  near  the  orifice  of  the  gland.  Cells 
such  as  have  been  described,  which  appear  like  cups  filled  with  mucus,  are 
known  as  goblet  cells. 

In  certain  stratified  or  pseudo-stratified  epithelia,  the  formation  of 
mucus  has  been  seen  to  take  place  in  some  of  the  deeper  cells,  but  the  dis- 
charge of  the  secretion  can  occur  only  when  these  cells  have  reached^  the 
free  surface. 

THE  NATURE  AND  CLASSIFICATION  OF  GLANDS. 

The  simplest  form  of  gland  is  merely  a  single  secreting  cell  situated 
apart  by  itself  in  an  epithelium.  Such  unicellular  glands  are  abundant 
in  invertebrates  and  are  represented  in  man  by  scattered  goblet  cells. 
In  the  higher  animals  the  secreting  cells  usually  occur  in  groups,  and  they 
are  generally  found  in  tubular  or  saccular  outpocketings  of  the  epithelium. 


Excretory  duct. 


Secretory  duct. 


Intercalated  duct- 


End  pieces. 

Fio.  47. — DIAGRAM  OF  VARIOUS  FORMS  OF  GLANDS. 
The  arrangement  of  ducts  in  D  is  that  of  the  human  submaxillary  gland. 

An  unbranched  tubular  gland  is  shown  in  vertical  section  in  Fig.  46,  and 
in  the  diagram,  Fig.  47,  A.  The  secreting  cells  maybe  distributed  through- 
out the  tube,  or  they  may  be  limited  to  the  lower  part.  In  such  cases 
the  upper  part  forms  the  duct  of  the  gland.  Sweat  glands  are.  unbranched 
tubes,  with  a  coiled  secreting  portion  in  the  deeper  part  of  the  skin, 
and  a  relatively  long  duct  which  conveys  the  secretion  to  the  surface. 
Many  glands  are  branched,  as  in  Fig.  47,  B.  The  main  stem  becomes 
the  duct,  and  the  characteristic  secretion  is  formed  in  saccular  or  tubular 
"  end  pieces." 


GLANDS  57 

Such  glands  as  have  been  described,  either  branched  or  unbranched, 
occur  in  great  numbers  as  constituent  parts  of  some  organ,  and  they  are 
classed  as  simple  glands.  The  sebaceous  and  sweat  glands  of  the  skin, 
intestinal  glands,  and  uterine  glands  are  examples  of  this  class.  Many 
glands  are  much  larger  than  these,  owing  to  the  fact  that  the  epithelial 
outgrowth  has  branched  repeatedly.  It  becomes  invested  with  a  con- 
nective tissue  capsule,  which  sends  partitions,  or  septa,  among  the  ramifi- 
cations of  the  epithelial  tube,  thus  dividing  the  gland  into  lobes  and  lob- 
ules. A  lobule  usually  contains  a  terminal  branch  of  the  duct  together 
with  the  cluster  of  end  pieces  which  empty  into  it.  The  large  glands  not 
only  have  a  connective  tissue  framework,  but  also  a  special  supply  of 
nerves,  blood  vessels  and  lymphatic  vessels.  Thus  they  form  independent 
organs,  and  they  are  classed  as  compound  glands.  They  include  the  liver, 
which  discharges  its  secretion  through  a  single  duct;  the  pancreas,  which 
is  formed  by  the  fusion  of  two  glands  and  therefore  has  primarily  two 
ducts;  and  many  smaller  organs,  like  the  pros- 
tate, which  is  a  compact  group  of  glands  each 
of  which  has  a  separate  duct. 

All  the  glands  thus  far  considered  are  alike 
in  being  outpocketings  of  epithelium.  Most  of 
them  develop  as  masses  or  cords  of  epithelial 
cells  which  later  acquire  a  central  cavity  or 
lumen.  The  secreting  cells  may  discharge  their 
products  from  their  free  surfaces  directly  into 
the  lumen;  or  the  secretion  may  enter  minute 
canals,  either  within  the  cells  (intracellular),  or  FlG  48 
between  the  cells  (intercellular).  Intercellular 
secretory  canals  (also  called  capillaries)  are 
found  in  the  serous  glands  of  the  tongue  and 

in  the  serous  portions  of  the  salivary  glands;  they  occur  also  in  the 
liver,  the  gastric  and  pyloric  glands,  sweat  glands,  lachrymal  gland  and 
bulbo-urethral  gland.  Various  forms  are  shown  in  the  right  half  of  the 
diagram  Fig.  48.  They  occur  where  two  or  more  cells  come  together 
and  consequently  they  are  in  relation  with  two  or  more  terminal  bars. 
In  longitudinal  sections  the  bars  may  be  seen  to  extend  downward  along 
the  canals.  Through  such  intercellular  canals  the  basal  cells  in  a  glandu- 
lar epithelium  may  discharge  their  secretion  into  the  central  cavity,  as 
shown  in  Fig.  48.  Intracellular  secretory  canals,  shown  in  the  left  half 
of  Fig.  48,  are  less  definite  in  outline,  and  are  never  in  relation  with  termi- 
nal bars.  They  may  be  transient  vacuoles  opening  at  the  surface.  Some- 
times they  anastomose  and  form  a  network  of  canals  within  the  cell.  They 
have  been  observed,  together  with  intercellular  canals,  in  the  sweat 


. 


58  HISTOLOGY 

glands,  the  liver,  and  the  gastric  glands.  There  are  apparently  no  secre- 
tory canals  in  any  mucous  gland,  and  they  have  not  been  found  in  the 
duodenal,  intestinal,  uterine  and  thyreoid  glands,  the  kidney  or  the 
hypophysis. 

The  ducts  have  a  clear-cut  lumen  and  are  typically  lined  with  a  very 
regular  epithelium,  showing  distinct  cell  boundaries.  The  cells  usually 
do  not  contain  the  rods,  granules  or  vacuoles  characteristic  of  secreting 
protoplasm,  and  the  nuclei  are  not  crowded  to  the  base  of  the  cells. 
In  some  cases,  however,  the  ducts  contain  mucous  cells,  and  in  the  sali- 
vary glands  a  specialized  portion  of  the  ducts  is  believed  to  discharge 
salts  into  the  secretion  as  it  passes  through  them.  In  such  a  gland 
(Fig.  47,  D)  the  duct,  as  it  leaves  the  end  pieces,  consists  of  simple  flat 
epithelium.  This  intercalated  duct  gives  place  to  the  secretory  duct  which 
is  lined  with  columnar  epithelium,  having  basal  rows  of  granules.  The 
outer  excretory  portion  consists  of  simple  or  stratified  non-glandular 
epithelium. 

The  end  pieces  of  the  glands,  as  already  noted,  vary  in  shape  from 
saccular  to  tubular.  Usually  a  minute  dissection  or  a  reconstruction  is 
necessary  to  determine  what  the  shape  may  be.  A  round  termination 
is  called  an  acinus  (Latin,  a  grape  or  berry)  or  an  alveolus  (Latin,  a  trough 
or  tray).  These  terms  are  often  used  interchangeably.  The  elongated 
forms  are  called  tubules. 

During  the  development  of  the  thyreoid  gland  the  duct  becomes 
obliterated,  so  that  the  secretion  within  the  end  pieces  cannot  escape. 
The  end  pieces  become  closed  epithelial  sacs,  known  as  follicles  (Latin, 
folliculus,  a  leather  bag,  shell,  or  husk).  In  addition  to  the  material 
enclosed  within  the  follicles,  the  thyreoid  gland  secretes  substances  which 
are  taken  up  by  the  surrounding  blood  vessels  and  lymphatic  vessels. 
Secretions  of  this  sort  are  called  internal  secretions. 

The  epithelioid  glands  are  masses  or  cords  of  cells  which  produce 
internal  secretions  only.  They  are  never  provided  with  a  duct  or  lumen, 
although  in  some  cases  their  cells  arise  from  the  wall  of  an  epithelial  tube. 
They  are  closely  related  to  the  glands  with  obliterated  ducts. 

Finally  there  are  glands  which  produce  cells  and  are  therefore  called 
cytogenic  glands.  These  include  the  ovary  and  testis,  which  are  epithelial 
structures  consisting  of  follicles  and  tubules  respectively.  They  produce 
the  ova  and  spermatozoa.  The  other  cytogenic  glands  are  non-epithelial 
bodies  which  produce  various  forms  of  blood  corpuscles.  They  will  be 
considered  in  a  later  chapter. 

The  classification  of  glands,  as  presented  in  the  preceding  paragraphs, 
is  summarized  in  the  following  table: 


GLANDS  59 

I.  Epithelial  glands,  with  persistent  ducts,  producing  external  secretions. 

1.  Unicellular  glands. 

2.  Simple  glands. 

a.  Ectodermal,  e.g.,  sweat  and  sebaceous  glands. 

b.  Mesodermal,  e.g.,  uterine  glands. 

c.  Entodermal,  e.g.,  gastric  and  intestinal  glands. 

3.  Compound  glands. 

a.  Ectodermal,  e.g.,  mammary  and  lachrymal  glands. 

b.  Mesodermal,  e.g.,  epididymis  and  kidney. 

c.  Entodermal,  e.g.,  pancreas  and  liver. 

II.  Epithelial  glands,  with  obliterated  ducts,  producing  internal  secretions. 

a.  Ectodermal,  anterior  lobe  of  the  hypophysis  (the  duct  of  the 

posterior  lobe  is  partially  obliterated). 

b.  Entodermal,  thyreoid  gland. 

III.  Epithelioid  glands,  never  having  duct  or  lumen,  producing  internal 
secretions. 

a.  Ectodermal  (through  their  relation  to  the  sympathetic  nerves), 

chromaffin  bodies;  and  medulla  of  the  suprarenal  gland. 

b.  Mesodermal,  cortex  of  suprarenal  gland;  interstitial  cells  of 

the  testis;  corpus  luteum. 

c.  Entodermal,  islands  of  the  pancreas;  epithelioid  bodies  in 

relation  with  the  thyreoid  gland;  thymus  (?) 

IV.  Cytogenic  glands,  producing  cells. 

a.  Mesodermal,  epithelial  —  the  ovary  and  testis. 

b.  Mesodermal,  mesenchymal  —  the  lymph  glands,  haemolymph 

glands,  spleen,  red  bone  marrow,  and  many  smaller  lymphoid 
structures. 

THE  MESENCHYMAL  TISSUES. 


Mesenchyma  (/xeW  middle,  ^yxvfjja)  an  infusion)  is  a  term  introduced 
by  0.  Her  twig,  in  1883,  for  the  tissue  produced  by  cells  which  have 
wandered  out  from  the  epithelial  germ  layers  into  the  spaces  between  them. 
It  is  found  only  in  young  embryos.  In  the  adult  it  is  represented  by  a 
large  group  of  derivatives,  including  connective  tissue,  adipose  tissue, 
cartilage,  bone,  smooth  muscle  fibers,  tendons,  fasciae,  and  various 
special  forms  of  cells.  Mesenchyma  arises  chiefly  from  different  parts 
of  the  mesoderm,  as  already  described  (p.  42),  but  in  the  head  of  the 
chick  embryo  a  portion  of  it  comes  from  the  ectoderm,  and  in  the  wall  of 
the  intestinal  tube,  according  to  Her  twig,  the  entoderm  contributes  to 
its  formation.  Together  with  the  blood  islands  it  constitutes  the  entire 
non-epithelial  tissue  of  the  embryo  in  early  stages.  It  consists  of  a  net- 


60  HISTOLOGY 

work  of  "branching  cells,  in  the  meshes  .of  which  there  is  a  homogeneous, 
fluid,  intercellular  substance.  The  intercellular  portion  of  the  tissue 
becomes  highly  developed  and  variously  modified. 

Although  typical  epithelium  and  mesenchyma  are  radically  different, 
as  shown-in  Fig.  31,  p.  42,  there  are  conditions  in  which  they  are  com- 
parable. Thus  dense  mesenchyma,  in  which  the  cells  are  closely  packed 
and  have  very  little  intercellular  substance,  resembles  epithelium,  and  it 
may  give  rise  to  groups  or  cords  of  epithelioid  cells.  Moreover  epithe- 
lium may  resemble  mesenchyma  by  forming  a  vacuolated  syncytium,  or 
as  seen  in  Fig.  49,  a  branching  protoplasmic  network.  In  epithelium  the 
intercellular  spaces  arise  as  vacuoles  in  the  exoplasm,  and  the  inter- 
cellular substance  of  mesenchyma  may  also  be  considered  as  occupying 
coalescent  vacuoles. 

Intercellular  spaces. 


Nuclei 


V 

Intercellular  bridges. 
FIG.  49. — FLAT  EPITHELIAL  CELLS  FROM  THE  BRANCHIAL  PLATE  OF  A  LARVAL  SALAMANDER.     X  300- 

The  tissue  of  the  adult  which  most  closely  resembles  mesenchyma  is 
known  as  reticular  tissue.  It  cannot,  however,  be  regarded  as  an  imma- 
ture connective  tissue,  or  a  persistence  of  the  primitive  mesenchyma, 
since  it  arises  rather  late  in  embryonic  development  (e.g.,  in  the  lymph 
glands  which  first  appear  in  human  embryos  measuring  about  45  mm., 
and  in  the  oesophagus  of  embryos  of  30  mm.).  It  is  therefore  considered 
to  be  a  special  form  of  connective  tissue. 

RETICULAR  TISSUE. 

Reticular  tissue  forms  the  framework  of  lymph  glands,  red  bone 
marrow  and  the  spleen;  it  occurs  as  a  layer  immediately  beneath  the 
epithelium  of  the  digestive  tract,  and  has  been  reported  in  many  other 
organs.  It  consists  of  a  network  of  cells  in  relation  with  an  abundant 


RETICULAR   TISSUE 


6l 


fluid  intercellular  substance  (Fig.  50).  The  protoplasmic  processes  of 
the  primitive  mesenchyma  have  become  transformed  into  flattened  strands 
or  slender  fibers,  which  are  clear  and  homogeneous,  and  anastomose 
freely.  The  cells  associated  with  these  fibers  contain  pale,  flattened, 
oval  nuclei,  with  few  chromatin  granules.  In  ordinary  sections  reticular 
tissue  will  be  most  readily  recognized  by  the  cells  lodged  in  the  fluid  in- 
tercellular substance.  These  cells,  which  are  chiefly  lymphocytes,  having 
round  nuclei  and  a  narrow  rim  of  protoplasm,  are  often  so  abundant  that 
the  tissue  appears  as  a  dense  cellular  mass  in  which  the  framework  of 
reticular  tissue  is  almost  completely  hidden.  Upon  careful  examination, 
however,  some  of  its  nuclei  and  fibers  can  always  be  detected. 


FIG.  50. — RETICULAR  TISSUE  SEEN  IN  A  FROZEN  SECTION  OF  A  DOG'S  SPLEEN  WHICH  HAD  BEEN  INJECTED 
WITH  SILVER  NITRATE.     Xaso.     (Mall.) 
A,  artery  with  its  ampullae  (a);  V,  vein. 


In  order  to  study  reticular  tissue  advantageously,  the  lymphocytes 
and  other  forms  of  free  cells  should  be  disengaged  from  its  meshes.  This 
may  be  accomplished  by  shaking  or  brushing  the  sections;  or  by  arti- 
ficially digesting  the  specimen  (which  if  properly  done  will  destroy  the 
cells,  including  those  of  the  reticular  tissue,  but  will  leave  the  network 
of  fibers);  or  by  the  following  ingenious  method  devised  by  Mall.  A 
piece  of  fresh  spleen  is  distended  by  injecting  gelatin  into  its  substance; 
it  is  then  frozen  and  sectioned.  The  sections  are  put  in  warm  water,  which 
dissolves  out  the  gelatin,  carrying  the  loose  cells  with  it,  and  leaves  areas  of 
clear  reticular  tissue.  Professor  Mall  has  also  shown  how  to  wash  out  the 


62  HISTOLOGY 

pulpy  contents  of  the  entire  spleen,  so  as  to  leave  the  framework  of  con- 
nective and  recticular  tissue,  which  may  be  inflated,  and  dried  (Zeitschr. 
f.  Morph.,  1900,  vol.  2,  pp.  1-42).  Such  preparations  give  an  idea  of 
the  intricacy  of  the  reticular  meshwork  that  can  be  obtained  in  no  other 
way,  and  yet  the  finer  ramifications  have  been  destroyed  by  this  process. 

There  has  been  considerable  discussion  as  to  whether  the  fibers  of  reticular  tissue  are 
chemically  different  from  those  of  ordinary  connective  tissue.  They  differ  from  the 
elastic  elements  of  connective  tissue,  since  reticular  fibers  are  dissolved  by  both  acids 
and  alkalis  which  leave  the  elastic  fibers  intact;  and  they  are  not  destroyed  by  pancreatic 
digestion  which  causes  the  elastic  fibers  to  disintegrate.  But  the  differentiation  of  the 
reticular  fibers  from  the  "white  fibers"  of  connective  tissue  has  not  been  successfully 
accomplished.  Mall  has  shown,  however,  that  tendon,  consisting  largely  of  white  fibers, 
is  dissolved  more  readily  by  boiling  in  £  p.c.  solutions  of  potassium  hydrate  or  hydro- 
chloric acid,  respectively,  than  sections  of  lymph  glands;  and  the  name  reticulin  has 
been  introduced  for  a  constituent  of  the  reticular  fibers  which  does  not  yield  gelatin  on 
boiling.  Reticulin  is  not  generally  recognized  as  an  independent  substance,  and 
reticular  tissue  often  appears  to  blend  with  white  fibrous  connective  tissue. 
The  recognition  of  reticular  tissue  depends,  therefore,  on  its  form  rather  than  on 
its  chemical  constitution. 

Mucous  TISSUE. 

The  substance  of  the  umbilical  cord  is  composed  of  mucous  tissue. 
At  birth  it  is  a  peculiar  gelatinous  mass  of  pearly  luster,  which  has  long 
been  known  anatomically  as  Wharton's  jelly.  During  its  development 
from  mesenchyma,  a  large  amount  of  mucus  becomes  deposited  in  its 
intercellular  spaces.  This  mucus,  like  that  produced  in  the  goblet  cells 
and  that  found  in  the  cornea  and  vitreous  body  of  the  eye,  is  a  trans- 
lucent substance  which  contains  mucin.  Chemically  there  are  many 
varieties  of  mucins.  They  are  compound  protein  bodies  containing  a 
carbohydrate  complex  in  their  molecules,  and  are  therefore  known  as 
glycoproteins.  True  mucins  are  formed  in  abundance  in  goblet  cells  and 
in  mucous  tissue;  to  a  less  extent  they  occur  in  all  embryonic  connective 
tissue.  Related  substances,  called  mucoids,  have  been  obtained  from 
tendon,  cartilage  and  bone. 

In  the  umbilical  cord  the  mucus  may  be  regarded  as  a  secretion  which 
is  produced  without  the  formation  of  special  granules  or  vacuoles,  and  is 
discharged  equally  from  all  surfaces  of  the  cells.  It  is  a  homogeneous 
ground-substance,  in  which  extremely  delicate  fibrils  are  imbedded.  These 
are  gathered  in  wavy  bundles  (Fig.  51,  a).  Fibrils  of  the  same  sort, 
generally  arranged  in  denser  bundles,  are  found  in  ordinary  connective 
tissue,  and  constitute  the  white  fibers.  Chemically  they  are  said  to  con- 
sist of  collagen,  an  albuminoid  body  which  on  boiling  yields  gelatin,  the 
source  of  glue.  The  origin  of  the  collagenous  fibers  has  been  the  subject 
of  repeated  investigation.  Henle  (1841)  considered  that  they  arose  in 


MUCOUS   TISSUE  63 

the  intercellular  substance,  apart  from  the  cells,  and  Merkel  defends  this 
idea  in  the  following  passage,  here  somewhat  abbreviated  (Anat.  Hefte, 
Abt.  i,  1909,  vol.  38,  pp.  323-392): 

The  mesenchymal  syncytium  secretes  an  amorphous  gelatinous  substance,  which 
may  be  scanty  (as  in  reticular  tissue)  or  abundant  (as  in  the  umbilical  cord) .  The  fibers 
arise  exclusively  in  this  gelatinous  substance;  the  cells  take  no  direct  part  in  the  forma- 
tion of  the  fibers  but  serve  only  for  the  production  of  the  jelly.  At  their  first  appearance 
the  fibers  are  not  collagen,  and  generally  they  are  not  yet  smooth  and  glistening  like 
true  connective  tissue  fibers.  Instead  they  are  granular,  and  not  infrequently  varicose. 
Later,  though  often  very  soon,  they  acquire  the  characteristic  appearance  of  fully 


a— - 


FIG.  51. — Mucous  TISSUE  OF  THE  HUMAN  UMBILICAL  CORD,  STAINED  WITH  PHOSPHO-TUNGSTIC  ACID 

H^EMATOXYLIN.     (Mallory.) 
a,  White  fiber,     b,  fibroglia. 


formed  connective  tissue  fibers.  They  may  arise  as  a  very  delicate  network,  which, 
through  the  breaking  down  of  the  least  utilized  threads,  becomes  transformed  into 
smooth  and  unbranched  fibers.  But  in  places  where  from  the  first  there  is  a  decided 
stretching,  as  in  tendon,  parallel  unbranched  fibers  are  formed  directly.  Professor 
Heiderich  has  shown  me  preparations  of  a  mucin,  in  which,  by  the  addition  of  acid, 
structures  were  formed  which  were  strikingly  similar  to  developing  connective  tissue — 
without  any  stretching,  nets  with  round  meshes;  but  with  the  slightest  traction,  long 
fibers  isolated  from  one  another.  Thus  connective  tissue  fibers  are  merely  the  effects 
of  mechanical  conditions  upon  the  gelatinous  intercellular  substance. 

A  very  different  idea  of  the  origin  of  the  white  fibers  is  that  of  Flem- 
ming,  recently  further  elaborated  by  Meves  (Arch.  f.  mikr.  Anat.,  1910, 
vol.  75,  pp.  149-208),  according  to  whom  the  fibers  arise  within  the  cyto- 
plasm. By  special  methods  Meves  has  demonstrated  coarse  filaments, 
which  he  names  chondrioconta,  within  the  protoplasm  of  both  epithelium 
and  mesenchyma.  These  granule-rods  or  chondrioconta  (probably 
comparable  with  the  mitochondria  of  gland  cells)  are  regarded  as  a  part 
of  the  fundamental  protoplasmic  network  or  spongioplasm.  If  they 
are  short  they  are  called  chondriosomes.  Meves  describes  the  develop- 
ment of  white  fibers  as  follows: 


64  HISTOLOGY 

Connective  tissue  fibrils  are  produced  from  the  chondrioconta  which  come  to  lie  at 
the  surface  of  the  cell.  They  then  change  their  chemical  constitution  and  are  no  longer 
stained  by  iron  haematoxylin  or  fuchsin.  At  this  stage  those  which  are  in  a  row  unite 
end  to  end.  Thus  in  the  formation  of  a  fibril  numerous  cells  take  part,  each  producing 
a  section.  The  fibrils  again  change  their  chemical  constitution  and  become  intensely 
stained  by  the  collagen  stains.  Finally  they  become  free  from  the  cells  and  lie  in  the 
intercellular  spaces.  From  the  time  of  their  first  formation  they  have  a  wavy  course, 
which  may  become  more  marked  later.  This  clearly  means  that  the  connective  tissue 
fibers  have  grown  in  length  more  than  the  surrounding  elements.  They  increase  also 
in  diameter  through  independent  growth,  and  for  a  time  new  fibers  are  produced  by  the 

cells I  differ  with  Flemming  since  I  consider  that  connective  tissue  fibers 

are  not  formed  within  the  cell  body  but  are  produced  at  the  cell  surface  (by  transforma- 
tion of  the  chondrioconta) ;  I  agree  with  him  in  deriving  them  from  the  cytoplasmic 
filaments. 

The  umbilical  cord  has  long  been  regarded  as  a  particularly  favorable 
object  for  the  study  of  white  fibers,  but  the  way  in  which  they  arise  remains 
undetermined.  In  addition  to  these  white  fibers,  the  umbilical  cord  con- 
tains stiff  fibers  of  a  different  nature,  found  at  the  periphery  of  the  cells. 
They  are  similar  to  the  fibers  of  a  tissue  which  forms -the  framework  for 
the  branching  nerve  cells,  thus  binding  them  together,  and  accordingly 
named  neuroglia  (vefyov,  nerve,  yAux,  glue).  Fibers  similar  to  those 
of  the  neuroglia,  found  at  the  periphery  of  muscle  cells,  are  called  border 
fibrils  or  myoglia.  In  1903  Mallory  described  similar  border  fibrils  in 
connective  tissue  and  named  them  fibroglia.  They  are  seen  at  the  peri- 
phery of  the  cells  in  the  umbilical  cord  (Fig.  51,  b).  Mallory  describes 
them  as  follows  (Journ.  Med.  Res.,  1905,  vol.  13,  pp.  113-136): 

Neuroglia,  myoglia  and  fibroglia  fibrils  morphologically  and  in  certain  staining 
reactions  more  or  less  closely  resemble  one  another.  They  touch  or  form  part  of  the 
periphery  of  the  cell  protoplasm,  but  continue  away  from  the  cell  in  two  directions,  i.e., 
they  do  not  begin  or  end  in  the  cell  which  produces  them.  How  far  the  fibroglia  are 
accompanied  by  protoplasmic  processes  cannot  be  determined.  The  number  of  these 
fibrils  to  a  cell  is  not  constant,  but  it  is  usually  in  the  neighborhood  of  a  dozen. 

Professor  Mallory  has  found  no  transitions  between  the  fibroglia  and 
the  white  fibers.  Meves  likewise  considers  them  as  entirely  distinct, 
and  states  that  the  production  of  white  fibers  by  the  cells  of  the  umbilical 
cord  terminates  by  the  fifth  month.  The  fibroglia  are  present  at  birth, 
and  probably  no  tissue  is  more  favorable  for  their  study  than  the  umbilical 
cord  at  term. 

In  addition  to  the  mucous  matrix,  the  white  fibers,  and  the  fibroglia, 
mucous  tissue  contains  cells  and  intercellular  spaces.  The  cells,  at  first 
stellate  with  many  anastomoses,  become  elongated  and  more  or  less  dis- 
connected from  one  another.  Three  of  their  nuclei  are  shown  in  Fig.  51, 
but  their  cytoplasm  forms  a  thin  layer,  the  limits  of  which  can  scarcely 
be  determined.  The  intercellular  spaces  contain  a  fluid  through  which 


CONNECTIVE    TISSUE  65 

cells  may  migrate.  There  are  no  capillaries,  lymphatic  vessels,  or  nerves 
within1  the  mucous  tissue  of  the  umbilical  cord,  and  no  elastic  fibers.  The 
three*  large  blood  vessels  which  pass  through  the  cord,  and  the  tissue  in 
their  walls,  will  be  considered  later. 

CONNECTIVE  TISSUE. 

Connective  tissue  occurs  in  various  forms.  Dense  connective  tissue 
is  a  tough  fibrous  substance,  such  as  that  part  of  the  skin  from  which  leather 
is  made;  and  loose  connective  tissue,  or  areolar  tissue,  is  a  spongy  cobweb 
of  delicate  filaments,  such  as  occurs  between  the  muscles.  Both  forms 
when  fresh  are  very  white,  and  they  are  composed  of  similar  fibers.  A 
small1  mass  of  fresh  connective  tissue,  subcutaneous  or  inter-muscular, 
may  be  spread  out  with  needles  upon  a  slide,  thus  forming  a  thin  film. 
After  adding  a  drop  of  water  and  applying  a  cover  glass,  it  will  present 

•K^MJ  .  x ' .        1 


FIG.  52. — SUBCUTANEOUS  TISSUE  FROM  A  CAT. 

The  fiber  a  has  been  treated  with  dilute  acetic  acid;  the  other  fibers  have  been  teased  apart  and  examined, 
unstained,  in  water,    a,  c,  White  fibers;  b,  fat  cell;  d,  connective  tissue  cell;  e,  elastic  fibers. 

such  an  appearance  as  shown  in  Fig.  52.  The  bulk  of  the  tissue  is  seen 
to  consist  of  white  or  collagenous  fibers  felted  together  (Fig.  52,  c).  They 
are  the  same  in  origin  and  structure  as  those  already  described  in  the 
mucous  tissue  of  the  umbilical  cord,  but  in  ordinary  connective  tissue 
their  fibrils  are  gathered  into  denser  bundles.  Each  bundle  or  fiber  is 
composed  of  exceedingly  minute  fibrils,  bound  together  by  a  small  amount 
of  cement  substance.  The  addition  of  picric  acid  causes  the  fibers  to 
separate  into  their  constituent  elements.  Often  a  bundle  of  fibrils  turns 
aside  from  the  main  trunk,  so  that  the  fiber  branches,  but  the  fibrils 
themselves  are  unbranched. 

Upon  the  addition  of  dilute  acetic  acid  the  white  fibers  swell  and  dis- 
integrate, some  of  them  passing  through  the  condition  shown  in  Fig.  52,  a. 
Such  fibers  show  a  succession  of  constrictions  at  places  where  they  are 
encircled  by  rings  or  spiral  bands  of  a  refractive  substance  not  affected 

5 


66 


HISTOLOGY 


X 


I 


\ 


B 


by  the  acid.  These  rings  have  been  observed  by  Ranvier  in  living  con- 
nective tissue  fibers,  and  it  is  therefore  improbable  that  they  are  remnants 
of  a  sheath  which  surrounded  the  entire  fiber,  as  some  have  thought. 
They  are  probably  formed  of  elastic  substance. 

In  addition  to  the  white  or  collagenous  fibers,  connective  tissue  con- 
tains fibers  of  a  second  sort,  known  as  elastic  fibers.  They  are  absent  from 
corneal  tissue,  the  mucous  tissue  of  the  umbilical  cord  and  generally, 
though  not  always,  from  reticular  tissue.  Since  they  develop  later  than 
the  white  fibers,  they  are  not  found  in  young  connective  tissue;  but  other- 

Awise  they  are  present,  though  varying 
greatly  in  abundance,  in  all  forms  of  con- 
* 
nective  tissue.  They  are  not  destroyed 
by  dilute  acids  or  alkalies,  and  are  de- 
scribed as  composed  of  elastin,  an  albumi- 
noid body  which  does  not  yield  gelatin  on 
boiling.  Unlike  the  white  fibers  they  are 
not  composed  of  smaller  elements  or  fibrils, 
but  each  fiber  is  a  structureless  homogen- 
eous thread.  In  favorable  cases,  however, 
an  enveloping  sheath  may  be  seen.  In 
tissue  which  has  not  been  torn  apart  the 
elastic  fibers  form  a  net  (Fig.  53,  A).  The 
fibers  meet  and  fuse  with  one  another;  and 
across  the  angles  thus  formed,  one  or  two 
delicate  strands  are  commonly  to  be  found.  When  the  tissue  is  pulled 
apart  so  that  the  net  is  bjoken,  the  fibers  kink  and  recoil  like  tense  wires 
(Fig.  52,  e). 

The  origin  of  the  elastic  fibers  has  not  been  determined.  They  have 
been  said  to  arise  within  the  cells  by  the  fusion  of  granules  of  elastin. 
Mall's  idea  of  their  exoplasmic  origin  is  illustrated  by  their  relation  to  the 
cells  in  Fig.  53,  B.  Others  consider  that  they  are  formed  from  the  inter- 
cellular substance. 

Although  elastic  fibers  are  clearly  seen  in  fresh  connective  tissue, 
they  are  often  invisible  in  specimens  stained  with  haematoxylin  and  eosin. 
In  order  to  determine  their  presence,  sections  may  be  stained  with  re- 
sorcin-fuchsin,  which  leaves  the  white  fibers  nearly  colorless,  but  makes 
the  elastic  fibers  dark  purple;  or  other  special  stains  may  be  used.  In 
some  situations,  however,  the  elastic  tissue  is  highly  developed  and  may 
be  seen  with  any  stain.  This  is  true  of  the  fenestrated  membranes  found 
in  many  blood  vessels.  A  fenestrated  membrane  is  a  network  of  elastic 
fibers  in  which  the  fibers  are  so  broad  that  they  appear  to  form  a  perfor- 
ated plate  (Fig.  54,  A).  The  greatest  development  of  elastic  tissue  prob- 
ably occurs  in  the  ligament  of  the  neck  in  grazing  animals,  which  consists 


FIG.  53. 

A,  Elastic  fibers  of  the  subcutaneous  areo- 
lar  tissue  of  a  rabbit.  e  (After  Schafer.) 
B,  Cells  in  relation  with  elastic  fibers, 
after  treatment  with  acetic  acid.  Sub- 
cutaneous tissue  of  a  pig  embryo. 
(After  Mall.) 


CONNECTIVE    TISSUE 


67 


of  very  coarse  elastic  fibers  with  very  little  white  fiber.  It  is  therefore  com- 
monly used  for  the  histological  and  chemical  study  of  elastic  tissue  (Fig. 
54,  B  and  C).  In  man  the  stylohyoid  ligament  and  the  ligamenta  flava 
are  of  this  class,  and  they  exhibit  the  yellowish  color  which  is  character- 
istic of  elastic  tissue.  Elastic  fibers  are  found  also  in  the  ground  substance 
of  certain  cartilages,  which  will  be  described  later. 

Connective  Tissue  Cells.  In  addition  to  white  collagenous  fibers  and 
yellow  elastic  fibers,  connective  tissue  contains  cells  and  intercellular 
spaces.  The  cells  which  produce  fibers  are  known  as  fibroblasts  (^Aao-ros, 
a  bud,  is  used  in  many  terms  to  indicate  a  formative  cell,  with  a  prefix 
which  usually  designates  the  structure  which  it  produces).  Actively 


FIG.  54. — ELASTIC  FIBERS. 

A,  Network  of  thick  elastic  fibers  below,  passing  into  a  fenestrated  membrane  above.  From  the  human 
endocardium.  B,  Thick  elastic  fibers  (f)  from  the  ligamentum  nuchae  of  the  ox;  b,  white  fibers.  C, 
Cross  section  of  the  ligamentum  nuchae,  lettered  as  in  B. 

growing  fibroblasts,  both  in  the  embryo  and  in  the  adult,  exhibit  fibroglia 
fibrils  at  their  borders,  but  in  mature  connective  tissue  these  fibrils  are 
seldom  found.  The  cells  of  fully  formed  connective  tissue  are  generally 
flattened  or  lamellar,  consisting  of  a  thin  pale  layer  of  almost  homogeneous 
protoplasm,  which  is  sometimes  vacuolated.  Such  cells  when  seen  on 
edge  are  spindle-shaped.  They  may  be  spread  out  in  flat  layers,  retaining 
the  protoplasmic  connections  characteristic  of  mesenchyma,  as  seen  in  the 
mesentery  (Fig.  55,  c).  In  dense  connective  tissue  the  cells  also  exhibit 
broad  thin  protoplasmic  processes  (Fig.  56,  c),  but  they  have  become  more 
or  less  detached  from  one  another.  The  cells  are  bent  to  conform  with 
the  a'djacent  fibers,  to  which  they  are  closely  applied,  and  along  which, 
in  living  tissue,  they  have  been  observed  to  migrate.  The  nuclei  of  these 
cells  are  elliptical  on  surface  view,  and  rod-shaped  when  seen  on  edge. 
They  contain  fine  chromatin  granules,  and  sometimes  a  small  but  distinct 
nucleolus.  Occasionally  the  nuclei  are  indented  on  one  side.  The  centre- 


68 


HISTOLOGY 


some,  in  a  clear  area  of  protoplasm,  has  been  found  close  beside  the  nu- 
cleus. In  ordinary  specimens,  stained  with  haematoxylin  and  eosin,  the 
centrosome  is  not  seen,  and  the  entire  cytoplasm  is  quite  inconspicuous; 


V 


FIG.  35. — CONNECTIVE  TISSUE  CELLS  (c)  AND  A  MAST  CELL  (m  )FROM  THE  MESENTERY  OF  A  RAT.  X  1000; 
b.v.  a  small  blood  vessel  lined  with  endothelial  cells.     The  specimen  was  fixed  in  alcohol  and  stained  with 

Unna's  methylene  blue. 

but  the  nuclei  stand  out  prominently  along  the  edges  of  the  fibers  (Fig. 
56,  x). 

Cells  in  connective  tissue  which  differ  from  the  fibroblasts  by  having 
abundant  protoplasm  in  the  form  of  large  round  cell  bodies,  were  named 


FIG.  56. — CONNECTIVE  TISSUE  CELLS  (c)  A  LYMPHOCYTE  (1)  AND  PLASMA  CELLS  (p)  FROM  A  LACTATING 

HUMAN  BREAST.     X   1000. 
A  vacuolated  plasma  cell  is  shown  at  v,  and  a  connective  tissue  cell  on  edge  is  seen  at  x. 

plasma  cells  by  Waldeyer  (Arch.  f.  mikr.  Anat,  1875,  vol.  n,  pp.  176- 
194).  He  stated  that  they  develop  from  connective  tissue  cells,  and  are 
always  arranged  about  the  blood  vessels.  Two  years  later,  in  the  same 


CELLS   IN   CONNECTIVE   TISSUE  69 

journal,  Ehrlich  published  the  first  of  his  far-reaching  investigations  on 
the  effects  of  various  anilin  dyes  upon  protoplasm.  He  showed  that  the 
plasma  cells  found  near  the  vessels  in  the  mesentery  of  the  rat,  when 
stained  with  basic  dyes,  exhibit  very  coarsely  granular  protoplasm  (Fig. 
55,  m).  Further  studies  led  him  to  separate  these  granular  cells  from  the 
other  forms  of  plasma  cells.  He  was  inclined  to  believe  that  they  arose 
from  over-nourished  connective  tissue  cells,  and  accordingly  named  them 
mast  cells  (Mastzellen),  referring  to  the  mast  or  acorns  on  which  animals 
are  fattened  (Arch.  f.  PhysioL,  1879,  pp.  166-171).  In  another  com- 
munication in  the  same  volume  (pp.  571-579),  he  introduced  a  further 
subdivision  of  cells  which  may  be  alike  in  form  but  which  react  differ- 
ently to  the  anilin  dyes.  In  contrast  with  the  basic  granules  of  the  mast 
cells,  which  are  not  stained  with  the  acid  dye  eosin,  he  found  other  granules 
which  stain  deeply  with  eosin  but  do  not  respond  to  the  basic  dyes. 
These  granules  are  now  generally  known  as  eosinophilic,  and  the  cells 
which  contain  them  are  called  eosinophiles.  Mast  cell  granules  are  often 
referred  to  as  basophilic,  but  since  some  confusion  results  from  calling 
the  entire  cells  basophiles,  they  are  still  known  as  mast  cells.  Cells  of 
both  classes  are  found  in  the  circulating  blood,  and  will  be  described  with 
the  blood  corpuscles ;  both  kinds  are  found  also  in  the  intercellular  spaces 
of  connective  tissue.  It  is  known  that  various  forms  of  blood  corpuscles 
develop  in  the  reticular  tissue  of  lymph  glands  and  bone  marrow,  from 
which  they  enter  the  blood  vessels;  and  it  is  also  very  evident  that  cells 
leave  the  vessels  and  enter  the  intercellular  spaces  of  connective  tissue. 
There  has  been  endless  discussion  as  to  whether  the  eosinophiles  of  con- 
nective tissue  and  blood  are  the  same  sort  of  cell;  and  also  whether  the 
"mast  leucocytes"  in  the  vessels  and  the  mast  cells  in  the  surrounding 
tissue  are  identical.  Maximow  states  that  there  is  no  genetic  relation 
between  mast  cells  and  mast  leucocytes  in  the  adult,  but  "whether  in 
embryonic  life  they  are  likewise  independent  is  still  undecided."  As  to 
the  eosinophiles,  he  says:  Those  found  in  the  connective  tissue  are 
generally  eosinophilic  corpuscles  which  have  emigrated  from  the  vessels. 
"  Any  proof  of  a  local  origin  in  connective  tissue  is  lacking."  But  Weiden- 
reich  considers  that  eosinophilic  granules  are  derived  from  broken-down  red 
corpuscles,  which  are  taken  up  by  white  blood  corpuscles  and  by  con- 
nective tissue  cells,  both  of  which  become  thereby  eosinophilic. 

In  ordinary  sections  of  connective  tissue,  stained  with  haematoxylin 
and  eosin,  eosinophiles  are  seldom  overlooked,  because  of  the  brilliant 
color  of  their  granules.  Mast  cells,  however,  should  be  sought  for  in 
tissue  preserved  either  in  formalin  or  alcohol,  and  stained  with  Unna's 
polychrome  methylene  blue  or  some  other  basic  dye.  The  preparation 
shown  in  Fig.  55  is  a  portion  of  the  mesentery  preserved  by  being  tied 
across  the  end  of  a  short  glass  tube  and  immersed  in  alcohol.  The  tissue 


70  HISTOLOGY 

was  then  stained  with  methylene  blue,  and  mounted  without  being  sec- 
tioned. Most  of  it  is  colored  pale  blue,  but  the  granules  of  the  mast 
cells  are  deep  purple.  Such  granules,  which  assume  a  color  different  from 
that  of  the  stain  employed,  are  called  by  Ehrlich  metachromatic.  The 
granules  of  mast  cells  are  so  coarse  that  in  favorable  places,  when  examined 
with  an  immersion  lens,  they  can  readily  be  counted.  They  spread  over 
and  obscure  the  nucleus,  which  appears  as  a  pale  central  area. 

Mast  cells  and  eosinophiles  were  removed  by  Ehrlich  from  the  miscel- 
laneous group  of  plasma  cells  described  by  Waldeyer.  Another  type  of 
cell  was  discovered  in  syphilitic  connective  tissue  by  Cajal,  and  inde- 
pendently described  in  tuberculous  tissue  by  Unna  (Monatsch.  f.  prakt. 
DermatoL,  1891,  vol.  12,  pp.  296-317).  He  states  that  these  cells  (to 
which  the  name  plasma  cells  has  come  to  be  restricted)  arise  from  normal 
connective  tissue  cells  by  the  increase  and  rounding  off  of  the  cell  body. 
As  described  by  Unna,  the  granulation  of  the  protoplasm  is  so  fine  that 
even  with  the  highest  magnification  the  individual  granules  cannot  be  dis- 
tinctly recognized  as  such. 

Typical  plasma  cells  are  shown  in  Fig.  56,  p.  They  usually  have 
very  round  nuclei  with  characteristic  coarse  masses  of  deeply  staining 
chromatin.  These  masses  may  appear  as  wedge-shaped  bodies  with  their 
broad  ends  against  the  nuclear  membrane  so  that  they  resemble  the 
spokes  of  a  wheel  ("Radkern") ;  or  the  chromatin  blocks  may  suggest 
the  squares  of  a  checker-board.  The  nucleus  occupies  an  eccentric  posi- 
tion in  the  mass  of  dense  and  deeply  staining  protoplasm.  Specific  granul- 
ation, such  as  occurs  in  mast  cells  and  eosinophiles,  is  absent.  In  certain 
plasma  cells,  vacuoles  are  seen  (Fig.  56,  v)  which  contain  a  "  homogeneous, 
semifluid,  colloid-like  substance  which  has  a  strong  affinity  for  acid  dyes." 
If  the  affinity  for  such  dyes  has  become  well  marked,  these  vacuoles 
form  conspicuous  structures,  known  as  RussePs  bodies.  Usually  they 
are  regarded  as  degenerative  products,  but  some  investigators  consider 
them  as  secretions. 

Associated  with  plasma  cells,  lymphocytes  are  often  found  (Fig.  56,  1). 
These  cells  constitute  an  important  class  of  white  blood  corpuscles  or 
leucocytes.  They  differ  from  plasma  cells  in  having  only  a  small  rim 
of  pale  protoplasm  about  the  nucleus,  but  the  nuclei  of  these  two  sorts  of 
cells  are  very  similar.  Although  Ehrlich  (1904)  agreed  with  Unna  that 
only  one  source  for  the  plasma  cells  had  been  established,  "namely,  an 
origin  from  hyper trophied  connective  tissue  cells,"  many  authorities 
now  believe  that  they  develop  from  lymphoid  cells  or  lymphocytes. 
Councilman  expresses  this  opinion  as  follows  (Journ.  Exp.  Med.,  1898, 
vol.  3,  pp.  393-420): 

As  to  their  origin  I  hold  the  same  opinion  as  Marschalko,  that  they  are  derived  from 
lymphocytes.  In  the  kidney  they  enter  into  the  interstitial  tissue  by  emigration  from 


CELLS   IN   CONNECTIVE    TISSUE  71 

the  blood  vessels.  They  may  emigrate  from  the  vessels  as  plasma  cells,  or  they  may 
be  formed  from  emigrated  lymphoid  cells.  They  have  been  seen  in  the  act  of  emigra- 
tion and  the  shapes  of  many  of  the  cells  in  the  interstitial  tissue  can  leave  no  doubt  as 
to  their  amoeboid  character.  We  are  led  to  the  belief  that  the  plasma,  cells  have  their 
origin  in  the  lymphoid  cells  from  the  similarity  of  their  nuclei  to  those  of  lymphoid  cells 
and  from  the  presence  of  transitional  forms. 

Downey  (Folia  haemat,  191 i,  vol.  n,  pp.  275-314)  supplies  a  useful 
review  of  the  literature  of  plasma  cells,  and  expresses  his  opinion  that 
they  arise  from  several  sources. 

Plasma  cells  are  found  in  connection  with  chronic  inflammation  of 
many  sorts.  They  occur  normally  in  abundance  in  the  mucous  membrane 
of  the  digestive  tube  from  the  stomach  to  the  rectum,  and  they  may  be 
seen  in  bone  marrow  and  in  the  lymphoid  organs.  Occasional  plasma 
cells  may  be  expected  in  subcutaneous  tissue  and  in  the  breast. 

Reviewing  the  preceding  paragraphs  it  is  seen  that  connective  tissue 
contains  fibroblasts  or  connective  tissue  cells,  and  that  mast  cells,  eosino- 
philic  cells,  plasma  cells  and  lymphocytes  may  be  lodged  in  the  intercellu- 
lar spaces.  Except  the  plasma  cells,  which  probably  develop  from  lym- 
phocytes, these  are  all  comparable  with  forms  of  blood  corpuscles  normally 
found  within  the  vessels.  The  source  of  these  corpuscles  will  be  further 
considered  with  the  blood,  together  with  other  forms  which  sometimes 
leave  the  vessels  but  which  are  never  regarded  as  constituents  of  connect- 
ive tissue. 

In  the  connective  tissue  of  amphibia  and  mammals,  Ranvier  described  certain 
slender  branched  cells  which  he  named  dasmatocytes  (Arch.  d'Anat.  micr.,  1900,  vol.  3, 
pp.  1 2  2-139) .  This  term  refers  to  the  detachment  of  portions  of  their  processes,  which 
Ranvier  believed  took  place  normally  as  a  method  of  discharging  a  secretion.  The 
breaking  down  was  observed  chiefly  in  amphibian  cells  which  are  now  considered  to  be 
mast  cells.  Like  other  mast  cells  they  are  prone  to  distintegrate.  The  cells  in  mam- 
mals, to  which  Ranvier  referred,  are  regarded  by  Maximow  as  derived  from  wandering 
lymphocytes.  He  believes  that  these  may  send  out  several  processes,  or  become 
spindle-shaped,  thus  producing  "  dasmatocytes,"  but  since  this  name  is  inappropriate 
he  calls  them  resting  wandering-cells.  He  finds  that  they  contain  a  limited  number  of 
vacuoles  and  coarse  granules,  but  the  granules  are  said  to  differ  from  those  of  mast  cells 
(Arch.  f.  mikr.  Anat.,  1906,  vol.  67,  pp.  680-757).  The  significance  of  these  cells  is 
uncertain. 

Connective  tissue  contains  two  additional  types  of  cells,  which  are  so 
distinct  that  they  may  be  regarded  as  separate  tissues.  These  are  the 
pigment  cells  and  the  fat  cells;  the  latter  will  be  described  as  adipose 
tissue. 

Pigment  cells.  The  color  of  the  various  tissues  is  due  to  pigments, 
which  may  be  in  solution,  like  the  haemoglobin  in  red  blood  corpuscles  and 
the  lipochromes  in  fat;  or  they  may  occur  as  granules  imbedded  in  the 
protoplasm.  The  granules,  which  are  yellow,  brown,  or  black,  often 


72  HISTOLOGY 

retain  their  natural  color  in  stained  specimens.  They  are  said  to  consist 
of  "melanin,"  which  represents  an  ill-defined  group  of  substances,  some  of 
which  are  haemoglobin  derivatives.  In  the  lung,  inhaled  soot  is  taken 
into  the  protoplasm  of  certain  cells  which  thus  become  pigmented  with 
extraneous  material.  Pigment  granules  are  widely  distributed,  and 
may  be  found  in  the  liver,  spleen,  heart,  brain,  and  other  organs. 

In  certain  situations,  pigment  is  extensively  developed  in  branched 
connective  tissue  cells  such  as  are  shown  in  Fig.  57,  A.  In  man  these 
are  of  limited  occurrence,  being  found  near  the  eye,  and  in  the  pia 
mater,  especially  under  the  medulla  oblongata  and  upper  portion  of  the 

spinal  cord.  Weidenreich  con- 
siders that  this  represents  the 
remains  of  a  general  pigmented 
sheath  for  the  entire  nervous 
system.  In  lower  vertebrates 
branching  pigment  cells  are 
often  abundant  in  the  sub- 
cutaneous tissue,  and  changes 
Par£  Th"0  ?reeantofellharor?bSte  T$S±d  **  color,  such  as  occur  in  frogs, 

epithelium  from  the  conjunctiva  of  the  guinea-pig.  i  ,  •• 

The  pigment  is  chiefly  in  the  basal  layer.  are     due     to    the     extension    Or 

retraction  "of  these  processes. 

Such  pigmented  connective  tissue  cells  are  called  chromatophores  or 
chromatocytes.  But  in  the  human  skin  the  pigment  granules  are  in  the 
epidermis,  chiefly  in  the  basal  layers.  In  the  stratified  epithelium  of  the 
conjunctiva  of  the  eye,  toward  the  cornea,  numerous  pigment  granules 
are  found  in  the  basal  layers,  and  scattered  groups  occur  also  in  the  outer 
layers,  as  shown  in  Fig.  57,  B.  Pigment  in  this  situation  occurs  fre- 
quently in  the  Caucasian  race,  and  regularly  in  the  other  human  races. 
Simple  epithelium  may  be  densely  pigmented,  as  in  the  external  epithe- 
lium of  the  retina.  Thus  it  is  seen  that  pigment  cells  are  by  no  means 
limited  to  connective  tissue. 


ADIPOSE  TISSUE. 

If  in  a  freshly  killed  animal  a  loop  of  intestine  is  drawn  out  of  the 
abdominal  cavity,  the  blood  vessels  ramifying  in  its  mesentery  will  be 
seen  to  be  imbedded  in  a  band  of  fat,  which  branches  when  the  vessels 
branch,  and  diminishes  in  width  toward  the  intestine  as  the  vessels 
become  small.  The  close  relation  between  the  distribution  of  fat  and  the 
course  of  the  vessels  is  notable  also  in  sections.  Fat  cells  occur  in  groups 
or  lobules  around  the  vessels,  and  are  found,  with  few  exceptions,  wherever 
there  is  loose  connective  tissue.  They  may  also  occur  singly,  as  in  some 
parts  of  the  denser  connective  tissue  of  the  breast. 


ADIPOSE   TISSUE 


73 


When  examined  fresh,  each  fat  cell  appears  as  a  large  round  oil-drop, 
which  is  more  or  less  compressed  into  a  polyhedral  shape  by  the  sur- 
rounding cells.  It  is  highly  refractive,  having  a  border  which  becomes 
alternately  bright  and  dark  on  changing  the  focus.  The  liquid  fat  or 
oil  which  fills  the  cell,  leaving  only  an  imperceptible  film  of  protoplasm 
around  it,  may  escape  by  the  rupture  of  the  membrane,  thus  forming 
smaller  drops.  In  the  specimen  shown  in  Fig.  52  the  fat  was  seen  coming 
out  from  the  upper  surface  of  one  of  the  cells,  and  the  droplets  thus 
emerging  ran  together  forming  larger  ones.  As  fat  cells  develop, 
a  coalescence  of  small  drops  occurs  in  the  protoplasm. 

The  earliest  formation  of  adipose  tissue  is  said  to  occur  in  human 
embryos  of  the  fourth  month.  It  may  be  studied  advantageously  in 
the  subcutaneous  tissue  of  embryos  of  the  fifth  month  (Fig.  58).  In 
such  specimens  there  are  areas  of  loose  and  very  vascular  mesenchyma, 
found  at  the  level  of  the  roots  of  the  hairs,  in  which  certain  cells  exhibit 
vacuoles.  These  cells  are  at  first  quite  like  the  surrounding  fibroblasts, 


FIG.  58. — SUBCUTANEOUS  FAT  CELLS  FROM  A  HUMAN       FIG.  59. — FAT  CELLS  FROM  NEAR  THE  KIDNEY  OF 

EMBRYO  OF  THE  FIFTH  MONTH.     X  520.  A  NEW-BORN  CHILD.     X  520. 

n  Nucleus;  f.v.,  fat  vacuole;  p.  r.,  protoplasmic  rim. 

being  fusiform  or  stellate.  Their  protoplasm  contains  several  small 
vacuoles,  some  of  which  unite  to  form  one  large  drop,  and  the  nucleus 
together  with  the  greater  part  of  the  protoplasm,  is  pushed  to  one  side 
(Fig.  58,  n).  Sections  of  such  cells  have  the  form  of  "signet  rings." 
Frequently  small  vacuoles  are  seen  in  the  accumulation  of  protoplasm 
beside  the  nucleus.  With  further  development '  the  fat  droplet  becomes 
so  large  that  the  protoplasmic  rim  appears  as  a  mere  line  or  membrane, 
just  within  which  is  the  greatly  flattened  nucleus.  During  the  formation 
of  the  fat  cells,  the  branching  processes  become  very  short,  but  it  is 
doubtful  whether  they  are  altogether  lost. 

For  some  years  after  birth  fat  cells  containing  several  vacuoles  are 
found  in  certain  situations,  as  around  the  kidney  (Fig.  59)  and  in  the 
outer  layer  of  the  oesophagus.  Usually  these  are  regarded  as  immature 
forms. 

Adipose  tissue  of  the  adult,  when  well  preserved,  presents  cells  of 


74 


HISTOLOGY 


rounded  form  as  shown  in  Fig.  60;  often,  however,  their  thin  walls  are 
bent  or  collapsed.  If  the  sections  are  thick,  a  network  of  a  different ' 
pattern,  representing  another  layer  of  cells,  will  come  into  view  on  chang- 
ing the  focus.  The  nuclei  of  the  fat  cells  are  pale  oval  bodies,  with  finely 
granular  chromatin  (Fig.  60,  n),  often  containing  one  or  two  small  vacuoles. 
The  protoplasm  around  the  nucleus  forms  such  a  thin  layer  that  it  is 
scarcely  appreciable  on  surface  view.  Both  nucleus  and  protoplasm 
are  much  darker  when  seen  on  edge,  since  a  thicker  layer  of  substance  is 
thus  presented.  When  sectioned  in  this  position  the  nuclei  within  the 
cells  must  be  carefully  distinguished  from  those  of  the  connective  tissue 
just  outside.  Many  of  the  fat  cells  will  show  no  nuclei,  since  the  entire 
cell  is  usually  not  included  within  the  limits  of  one  section. 

In  extreme  emaciation,  the  fat  cells  become  small  and  the  protoplasmic 
rim  thickens,  so  that  the  cells  again  assume  the  signet-ring  form.     A 


FIG.  60. — 'NORMAL  ADIPOSE  TISSUE  FROM  AN  ADULT. 

X  400. 
Connective  tissue  is  seen  at  the  left  of  the  figure  and 

(as  at  c.  t.)  between  the  fat   cells;  n,   nucleus 

of  a  fat  cell.  4 


FIG.  61. — 'FAT  CELLS  FROM  THE  OMENTUM  IN  A 

CASE  OF  EXTREME  EMACIATION.     X  520. 

b.  v.,  blood  vessel;  f.  c.,  fat  cell. 


delicate  reticulum  appears  between  the  shrunken  cells  as  shown  in  Fig. 
61.  Some  of  the  fibers  proceed  directly  from  the  fat  cells,  indicating 
that  the  processes  have  never  wholly  disappeared.  Others  come  from 
the  fibroblasts  which  from  the  first  are  scattered  among  the  fat  cells. 

The  great  difference  between  the  appearance  of  fresh  fat  cells  and 
those  seen  in  sections  is  due  to  the  fact  that  fat  is  dissolved  by  the  reagents 
ordinarily  used  in  preserving  the  tissue.  Thus  the  sections  usually 
show  empty  vacuoles  and  no  fat  whatever.  Occasionally,  as  a  result 
of  cooling,  the  fat  has  formed  insoluble  crystals  in  the  shape  of  radiating 
needles,  and  these,  or  an  amorphous  precipitate  which  takes  a  bluish 
stain  with  haematoxylin,  may  be  seen  within  the  cells.  Although  fat 
is  the  commonest  substance  to  be  found  within  the  vacuoles  in  human 


ADIPOSE    TISSUE 

tissues,  it  is  not  the  only  material  which  may  have  filled  them,  and 
therefore  to  demonstrate  the  presence  of  fat,  special  methods  must  be 
employed.  Fresh  tissue  may  be  preserved  in  osmic  acid,  which  blackens 
not  only  fat  but  some  related  substances ;  or  frozen  sections  of  tissue  may 
be  stained  with  Sudan  III  or  Scharlach  R,  which  color  fat  droplets  red 
and  demonstrate  them  even  when  minute.  These  stains  may  also  be 
used  after  preservation  of  the  tissue  in  formalin.  It  may  be  noted  that 
Sudan  III  has  been  fed  to  animals,  thus  imparting  a  pink  color  to  the 
living  adipose  tissue.  If  the  animal  is  lactating,  the  fat  globules  in  the 
milk  also  become  pink. 

Fat  vacuoles  occur  in  many  sorts  of  cells  which  do  not  belong  to  adi- 
pose tissue,  such  as  the  cells  of  the  liver,  cartilage,  and  striated  muscle. 
These  cells  are  not  called  fat  cells,  even  if  their  protoplasm  contains  many 
vacuoles,  and  they  do  not  resemble  the  cells  of  adipose  tissue. 

Since  fat  cells  occur  in  lobular  masses  in  definite  places,  as  under  the  skin,  around 
the  kidney,  in  the  bone  marrow,  etc.,  and  since  they  supply  the  body  with  nutriment, 
it  has  been  proposed  to  regard  them  as  constituting  glandular  organs.  They  receive 
fat  from  the  adjacent  vessels  and  store  it,  or  quite  possibly  they  absorb  carbohydrates 
and  convert  them  into  fats.  The  formation  of  fat  has  been  said  to  begin  in  or  near 
the  nucleus  with  the  production  of  granules,  but  the  part  which  the  nucleus  plays 
is  uncertain.  The  small  vacuoles  often  seen  within  it  apparently  arise  after  the  cell 
is  full  of  fat.  Mast  cells  have  often  been  found  associated  with  fat  cells  and  it  has 
been  supposed  that  they  contained  secretory  granules  which  were  concerned  with 
fat  production.  Like  an  internal  secretion,  fat  is  taken  from  the  cells  into  the  vessels 
and  distributed  over  the  body. 

TENDON. 

Tendons  consist  essentially  of  very  dense  connective  tissue.  They 
are  composed  almost  wholly  of  parallel  white  or  collagenous  fibrils,  com- 


FIG.  62. — LONGITUDINAL   SECTION  OF  THE  FIG.  63. — TENDON  CELLS  FROM  THE  TAIL 

TENDON  OF  THE  FLEXOR  LONGUS  DIGITORUM.  OF  A  RAT.    STAINED  WITH  METHYLENE  BLUE, 

X  160.  INTRA  VITAM.    (Huber.) 

pactly  bound  together  in  bundles.  The  cementing  matrix  contains  lendo- 
mucoid.  Closely  applied  to  the  bundles  are  the  tendon  cells  which  pro- 
duced them.  In  ordinary  longitudinal  sections  of  tendon,  the  protoplasm 
of  the  cells  is  indistinct  or  imperceptible,  but  the  nuclei  appear  in  rows 
as  seen  in  Fig.  62.  In  special  preparations,  particularly  in  those  of  the 


76 


HISTOLOGY 


delicate  tendons  found  in  the  tail  of  a  rat  or  mouse  (Fig.  63),  it  is  seen  that 
the  cytoplasm  of  tendon  cells  forms  a  plate-like  layer  which  is  folded 
about  the  fiber  bundles,  tending  to  encircle  them.  Moreover  the  cells 
are  provided  with  lamellar  or  wing-like  projec- 
tions, which  extend  out  between  adjacent  fiber 
bundles.  Apparently  there  are  protoplasmic 
connections,  end  to  end,  between  the  cells,  which 
thus  form  longitudinal  rows  or  chains;  and  in 
cross  sections  of  the  tendon  some  of  the  wing-like 
projections  anastomose  as  seen  in  Fig.  64.  Thus, 
as  in  connective  tissue,  the  original  syncytial  ar- 
rangement of  the  mesenchyma  is  partially  pre- 
served. 

The  primary  tendon  bundles,  which  consist 
chiefly  of  white  fibers  and  tendon  cells,  contain 
also  a  small  amount  of  elastic  tissue  in  the  form  of 
fine,  wide-meshed  networks.  The  elastic  fibers 
are  said  to  occur  especially  near  the  cells  and  their 
processes.  The  primary  bundles  are  generally 
grouped  in  secondary  bundles  or  fasciculi,  which 
are  bounded  by  partitions  or  septa  of  looser  con- 
nective tissue  (Fig.  65).  Within  the  septa  there  are  nerves  and  blood 
vessels,  in  relatively  small  number.  Lymphatic  vessels  are  said  to  be 


FIG.  64. — FROM  THE  CALCA- 
NEAN  TENDON  (TENDO 
ACHILLIS)  OF  A  RABBIT. 
(After  Prenant.) 

p.  b.,  Primary  bundle  bounded 
by  a  cytoplasmic  sheath, 
sh.,  which  extends  from  a 
tendon  cell,  t.c.  p.,  process 
extending  into  a  primary 
bundle.  The  entire  figure 
is  a  portion  of  a  secondary 
bundle. 


Septum.          Blood  vessel.  Fasciculus.  Fibrous'sheath. 

FIG.  65. — FROM  A  CROSS  SECTION  OF  A  TENDON  FROM  AN  ADULT  MAN.     X  40. 

confined  to  the  sheath  of  connective  tissue  which  surrounds  the,  entire 
tendon,  with  which  the  septa  are  continuous  (Fig.  65). 

The  fibrous  sheath  or  vagina  fibrosa,  which  surrounds  the  tendon, 


TENDON 


77 


may  contain  a  cavity  filled  with  fluid.  It  is  then  called  a  mucous  sheath 
or  vagina  mucosa.  The  cavity  arises  as  a  cleft  in  the  embryonic  connective 
tissue  and  its  walls  are  formed  of  mesenchymal  epithelium.  The  cells 
have  become  flattened  and  the  fibers  felted  together  to  bound  the  space. 
It  contains  a  fluid  like  that  of  the  joint  cavities,  being  chiefly  water  and 
a  mucoid  substance  which  renders  it  viscid,  together  with  protein  material 
and  salts.  The  function  of  the  mucous  sheath  is  to  facilitate  the  move- 
ments of  the  tendon.  By  its  formation  the  tendon  is  freed  from  the  local 
connection  with  surrounding  tissue,  and  the  sheath  generally  occurs  where 
such  connection  would  especially  interfere  with  motion.  The  mucous 
burses  are  similar  structures  in  relation  with  muscles  or  bones.  The  joint 
cavities,  to  be  described  later,  belong  in  the  same  class,  having  a  similar 
origin  and  function. 

Aponeuroses,  fasciae  arid  ligaments  are  connective  tissue  formations, 
resembling  tendon  in  possessing  a  more  or  less  regular  arrangement  of 
cells  and  fibers.  Elastic  elements  may  be  abundant. 


Mes. 


Pre.Cart. 


Carl. 


CARTILAGE. 

Cartilage  is  a  mesenchymal  derivative,  the  development  of  which  it 
is  difficult  to  follow,  since  at  certain  stages  its  nuclei  are  so  crowded  that 
they  obscure  the  transformation  of  the  intercellular  substance.  Two 
interpretations  of  .its  develop- 
ment are  illustrated  in  Fig. 
66,  A  and  B.  As  represented 
in  A,  the  mesenchymal  cells 
multiply  and  come  together  so 
that  the  intercellular  spaces 
are  obliterated.  Thus  pre- 
cartilage is  formed,  consisting 
of  large  closely  adjacent  cells, 
separated  from  one  another  by 
thin  walls  which  stain  red 
with  eosin.  This  type  of  pre- 
cartilage  has  been  frequently 
described  in  the  lower  verte- 
brates. It  becomes  cartilage  by  the  thickening  and  chemical  transforma- 
tion of  its  exoplasmic  walls.  They  form  an  intercellular  ground  sub- 
stance or  matrix,  which  stains  blue  with  haematoxylin.  According  to 
Professor  Mall  the  same  result  is  produced  in  another  way,  as  shown  in 
Fig.  66,  B.  The  mesenchymal  cells  in  becoming  precartilage  produce  a 
fibrillated  exoplasm.  The  nuclei  with  the  surrounding  endoplasm  then 
become  "extruded  from  the  syncytium"  and  lie  in  the  intercellular  spaces. 


FIG.  66. — DIAGRAMS  OF  THE  DEVELOPMENT  OF  CARTILAGE 

FROM  MESENCHYMA. 

A,  Based  upon  Studnifika's  studies  of  fish;  B,  upon  Mall's 
study  of  mammals.  Mes..  Mesenchyma;  Pre.  Cart., 
precartilage;  Cart.,  cartilage. 


78  HISTOLOGY 

At  the  same  time  the  fibrillated  exoplasm  becomes  transformed  into  the 
homogeneous  matrix  of  the  cartilage,  which  stains  blue  with  haematoxylin. 
Whether  or  not  the  cells  are  extruded  may  be  questioned,  but  the  rela- 
tion of  the  fibrous  to  the  homogeneous  matrix,  which  is  shown  in  the 
figure,  may  readily  be  observed  around  the  vertebrae  in  pig  embryos. 

After  the  cartilage  has  formed,  the  cells  occupy  cavities,  or  lacuna,  in 
the  matrix.  It  is  probable  that  in  the  living  condition  the  cartilage  cells 
completely  fill  their  lacunae,  but  in  preserved  specimens  they  are  often 
irregularly  shrunken.  Usually  the  protoplasm  of  each  cell  is  of  a  spongy 
vacuolated  texture,  which  is  in  part  due  to  fat  droplets  and  in  part  to 
glycogen;  in  ordinary  sections,  both  of  these  substances  have  disappeared, 
leaving  empty  spaces. 

Glycogen  is  a  carbohydrate  which  resembles  starch  and  is  therefore  sometimes 
called  "animal  starch."  It  is  soluble  in  water,  and  soon  after  death  it  becomes 
converted  into  glucose.  For  both  of  these  reasons  it  disappears  from  ordinary  sec- 
tions. Fresh  tissues,  preserved  in  strong  alcohol  and  stained  with  tincture  of  iodine, 
exhibit  glycogen  as  brownish-red  granules  which  may  be  aggregated  in  masses  of 
considerable  size.  Glycogen  is  found  not  only  in  cartilage  cells  but  also  in  striated 
muscle  and  in  the  cells  of  the  liver.  In  the  embryo  it  has  a  wider  distribution.  At 
certain  stages  of  development,  according  to  Gage,  it  occurs  in  the  cells  of  the  nervous 
system  and  is  abundant  in  the  epidermis,  the  digestive  tube,  and  the  ccelomic  epithe- 
lium. Its  production,  like  that  of  fat,  varies  with  nutritive  conditions,  and  it  accumu- 
lates in  well-nourished  individuals. 

The  cartilage  cells  are  said  to  be  enclosed  in  capsules,  which  are  often 
transparent  and  inconspicuous  linings  of  the  lacunae.  Sometimes  they 
appear  as  rather  broad  bands  which  are  concentrically  striated,  indi- 
cating that  they  were  deposited  in  successive  layers.  The  layers  of  newly 
formed  matrix,  which  bound  the  lacunae,  usually  stain  very  dark  blue 
with  haematoxylin.  The  deep  color  is  probably  due  to  chondromucoid. 
Peripherally  the  color  blends  with  that  of  the  older  matrix,  which  takes 
a  pale  blue  stain.  Like  the  intercellular  substance  of  connective  tissue 
the  matrix  of  cartilage  may  contain  white  and  elastic  fibers,  but  in  its 
commonest  form  it  appears  homogeneous  and  hyaline.  Chemically  it  is 
a  mixture  of  collagen,  chondromucoid,  chondroitin  sulphuric  acid  in  com- 
bination, and  albuminoid  substances  (albumoid).  The  old  term  "chon- 
drin"  really  means  little  else  than  the  matrix  of  cartilage,  which  on  super- 
ficial examination  is  found  to  be  a  dense  body.  Within  it,  however,  the 
cells  produce  new  ground  substance  and  push  themselves  apart  from  one 
another  by  interstitial  growth.  The  cells  in  the  interior  of  the  cartilage 
are  often  much  larger  than  those  at  the  periphery,  and  the  increase  in 
the  size  of  their  lacunae  is  probably  accomplished  by  the  resorption  of  the 
adjacent  matrix.  The  cells  divide  by  mitosis,  and  after  division  two  of 
them  are  found  in  a  single  capsule.  They  then  move  apart,  and  a  parti- 
tion, at  first  very  slender,  is  formed  between  them.  They  may  remain 


CARTILAGE  79 

grouped  as  a  pair,  forming  a  bisected  elliptical  figure,  or  they  may  divide 
again,  producing  either  a  row  of  cells  or  a  cluster  of  three  or  four  (Fig. 
66).  Since  the  cells  change  their  positions  with  difficulty  in  the  dense 
matrix,  they  are  regularly  found  in  very  characteristic  groups.  It  has 
been  asserted  that  certain  cartilage  cells  undergo  mucoid  degeneration 
and  become  lost  in  the  matrix.  In  old  cartilage  dark  spots,  staining  in- 
tensely with  haematoxylin,  are  suggestive  of  such  a  process.  Such  cells 
must  be  carefully  distinguished  from  tangential  sections  of  the  deeply 
staining  pericapsular  matrix. 

Cartilage  grows  not  only  by  the  interstitial  increase  of  the  cells  and 
matrix  in  its  interior,  but  more  especially  by  appositional  growth,  through 

b^^^^-^^^^-      _*~"  ***Z  -x~~-*     ;^..   .,-    .^     vi^"* 


d — -r: 


rgr 

9  *>  ?.  **1  &?* 


A  B  C 

FIG.  67.— THE  THREE  TYPES  OF  CARTILAGE:  A,  HYALINE;  B,  ELASTIC;  C,  FIBROUS.     (Radasch). 

a,  b,  Outer  and  inner  layers  of  perichondrium ;  c,  young  cartilage  cells;  d,  older  cartilage  cells;  e,  f,  capsule 

surrounded  by  deeply  staining  matrix;  g,  lacuna. 

the  formation  of  new  cartilage  over  its  external  surface.  Around  every 
cartilage  in  the  adult,  there  is  a  connective  tissue  envelope,  the  perichon- 
drium, containing  undifferentiated  cells  which  multiply  and  become 
transformed  into  cartilage  cells  (Fig.  67,  A).  These  are  added  at  the 
surface,  undergoing  in  a  thin  layer  such  changes  as  are  shown  in  Fig.  66. 
The  young  generations  of  cells  are  therefore  at  the  periphery  of  the 
cartilage,  and  the  oldest  cells,  or  the  groups  which  they  have  produced, 
are  in  the  center.  Between  them  an  interesting  series  of  cytomorphic 
changes  may  be  observed.  Since  the  perichondrium  is  the  formative 
layer,  a  more  or  less  perfect  regeneration  of  cartilage  may  occur  after 
surgical  operations  if  the  perichondrium  is  left  in  place,  but  not  otherwise. 
The  perichondrium  contains  vessels  and  nerves,  none  of  which  pene- 


80  HISTOLOGY 

trate  the  matrix  of  the  cartilage.  In  some  cases,  however,  vascular  con- 
nective tissue  occupies  an  excavation  in  its  peripheral  portion.  What- 
ever nutriment  the  cells  in  the  interior  of  the  cartilage  receive  is  obtained 
by  diffusion  through  the  matrix.  It  has  been  asserted  that  this  diffusion 
takes  place  through  a  system  of  canals  penetrating  the  matrix,  and  pass- 
ing from  one  lacuna  to  another  as  in  bone.  But  in  mammalian  carti- 
lage the  only  canals  which  have  been  recorded  are  presumably  the  re- 
sult of  shrinkage,  such  as  may  be  produced  by  treating  the  specimen 
with  absolute  alcohol  or  ether. 

The  three  principal  forms  of  cartilage — hyaline,  elastic,  and  fibro- 
cartilage — and  the  exceptional  "vesicular  supporting  tissue"  may  be 
further  described  as  follows: 

Hyaline  cartilage,  the  commonest  type,  is  characterized  by  its  clear, 
pale  bluish  or  pearly  translucent  matrix,  which  is  ordinarily  free  from 
fibrils.  The  nasal  cartilages,  most  of  the  laryngeal  cartilages,  and  the 
tracheal  and  bronchial  rings  are  of  this  variety,  together  with  the  xiphoid 
and  costal  cartilages,  and  the  articular  cartilages  which  cover  the  joint 
surfaces  of  the  bones.  In  embryos  the  greater  portion  of  the  skeleton 
is  at  first  formed  of  hyaline  cartilage.  Although  the  matrix  usually  ap- 
pears homogeneous,  it  may  be  resolved  into  bundles  of  parallel  fibers  by 
artificial  digestion,  and  its  behavior  toward  polarized  light  indicates  an 
underlying  fibrillar  structure.  Sometimes,  as  a  degenerative  process,  a 
network  of  fibers  may  appear  in  the  matrix,  staining  red  with  eosin,  and 
resembling  the  elastic  fibers  shown  in  Fig.  68,  3.  Such  a  condition  has 
been  observed  in  the  trachea.  In  degenerating  portions  of  the  laryngeal 
and  costal  cartilages,  fibers  having  a  luster  like  asbestos  (or  the  mineral 
amianthus)  are  sometimes  seen;  according  to  Prenant  these  "amianthoid 
fibers "  are  neither  white  nor  elastic.  In  old  age  a  deposit  of  calcareous 
granules  often  occurs  in  the  matrix  of  hyaline  cartilage,  and  in  some  of 
the  laryngeal  cartilages  this  change  may  begin  by  the  twentieth  year. 
With  the  increase  and  coalescence  of  the  granules,  the  cartilage  becomes 
calcified,  and  blood  vessels  may  enter  it;  but  it  does  not  form  true  bone. 
As  with  other  calcified  structures,  such  as  tendon,  treatment  with  acids 
shows  that  the  underlying  tissue  has  retained  its  characteristic  features, 
and  remains  quite  different  from  bone. 

Elastic  cartilage  contains,  in  its  matrix,  granules,  fibers  or  networks 
of  elastic  substance  (Figs.  67,  B,  and  68) ;  consequently  its  color  is  yellowish. 
It  is  found  in  the  external  ear,  the  auditory  (Eustachian)  tube,  the  epi- 
glottis, and  in  certain  small  cartilages  of  the  larynx,  namely  the  cornicu- 
late  and  cuneiform  cartilages  and  the  vocal  processes  of  the  arytaenoid 
cartilages.  It  develops  from  hyaline  cartilage,  which  it  closely  resembles. 
Within  its  matrix,  granules  of  elastic  material  are  deposited,  which 
later  coalesce  to  form  fibers.  Some  authorities  have  stated  that  they 


CARTILAGE 


8l 


arise  from  the  cells,  but  according  to  Schafer  "  their  formation  apart 
from  the  cells  can  be  easily  verified  in  the  arytaenoid  cartilage  of  the  calf." 
The  elastic  nature  of  fibers  within  the  cartilage  matrix  can  be  demon- 
strated by  special  stains,  such  as  resorcin-f uchsin ;  they  stain  like  the  elastic 
fibers  of  connective  tissue. 


FIG.  68. — ELASTIC  CARTILAGE.     X  240. 

I,  Portion  of  a  section  of  the  vocal  process  of  an  arytaenoid  cartilage  of  a  woman  thirty  years  old;  the  elastic 
substance  is  in  the  form  of  granules.  2  and  3,  Portions  of  sections  of  the  epiglottis  of  a  woman  sixty 
years  old;  a  fine  network  of  elastic  fibers  in  2,  a  denser  network  in  3.  z,  Cartilage-cell,  nucleus  invisible; 
k,  transparent  capsule. 

Fibro-cartilage  cannot  be  regarded,  like  elastic  cartilage,  as  a  late  modi- 
fication of  hyaline  cartilage.  In  its  early  development,  as  seen  in  the 
intervertebral  disc  of  an  embryo,  its  matrix  is  primarily  fibrous.  It  is 
composed  of  anastomosing  bundles  of  fibers  which  blend  with  the  hyaline 
matrix  of  the  adjacent  vertebral  cartilage  as  shown  in  Fig.  66,  B.  Instead 
of  becoming  transformed  into  hyaline 
cartilage,  however,  it  develops  into  a 
cartilaginous  modification  of  dense  con- 
nective tissue.  It  is  found  typically  de- 
veloped in  the  intervertebral  and  inter- 
pubic  fibro-cartilages.  According  to  Stohr 
it  forms  the  articular  cartilage  lining  the 
sterno-clavicular,  acromio-clavicular,  and 
mandibular  joints,  together  with  the  joints 
of  the  costal  cartilages,  and  it  covers  the 
head  of  the  ulna.  Usually  it  is  said  to 
form  the  rims  deepening  the  sockets  of  the 
shoulder  and  hip  joints,  together  with  the 
interarticular  discsr  of  the  mandibular, 
sterno-clavicular  and  knee  joints  but  these,  according  to  Stohr,  consist  of 
dense  connective  tissue  without  the  characteristic  cartilaginous  matrix.  A 
portion  of  their  cells  are  round,  however.  Even  when  typically  developed, 
fibro-cartilage  consists  chiefly  of  interwoven  bundles  of  white  fibers. 
With  haematoxylin  and  eosin  this  ground  substance  is  diffusely  stained, 
since  the  fibers,  colored  by  the  eosin,  are  imbedded  in  a  chondro-mucoid 

6 


FIG.  69. — FROM  A  HORIZONTAL  SECTION 
OF  THE  INTERVERTEBRAL  Disc  OF  MAN. 

g,  Fibrillar  connective  tissue;  z,  cartilage- 
cell  (nucleus  invisible);  k,  capsule 
surrounded  by  calcareous  granules. 
X  240. 


82  HISTOLOGY 

matrix  which  stains  with  haematoxylin.  The  cells  are  not  flattened  as  in 
connective  tissue.  They  are  lodged  in  well-rounded  lacunae  (Fig.  69), 
bounded  by  capsules  and  zones  of  blue-staining  matrix;  and  they  are  fre- 
quently arranged  in  pairs  or  small  groups  such  as  occur  in  other  forms 
of  cartilage.  Their  protoplasm  is  extensively  vacuolated  and  is  some- 
times shrunken. 

"Vesicular  supporting  tissue"  is  a  form  of  precartilage  which  consists 
of  large  vesicular  cells  in  close  contact,  bound  together  by  firm  walls;  it 
is  a  "  cartilage  without  a  matrix. "  In  many  invertebrates  it  is  an  impor- 
tant tissue,  but  in  adult  mammals  it  is  of  limited  occurrence.  In  man 
such  a  tissue  is  said  to  be  present  on  the  inner  surface  of  the  tendon  of 
insertion  of  the  M.  quadriceps  femoris,  and  in  the  sesamoid  cartilage  in 
the  tendon  of  the  M.  peronaeus  longus.  This  form  of  cartilage  resembles 
the  notochordal  tissue  at  a  certain  stage  of  development,  and  it  is  called 
"chordoid  tissue"  by  ScharTer. 

NOTOCHORDAL   TISSUE. 

Although  the  notochord  is  of  entodermal  origin  (cf.  p.  38),  it  gives 
rise  to  a  tissue  which  has  often  been  called  cartilage.  Notochordal  tissue 


FIG.  70. — A  PORTION  OF  A  NUCLEUS  PULPOSUS  FROM  A  HUMAN  EMBRYO  OF  THE  SIXTH  MONTH.     X  225. 

The  notochordal  syncytium  is  seen  in  the  center  of  a  mucoid  matrix.     The  vertebrae  are  toward  the  right 

and  left,  beyond  the  limits  of  the  figure. 

differs,  however,  from  any  of  the  types  thus  far  considered.  The  principal 
stages  in  its  development  in  the  pig  have  been  described  by  Williams 
(Amer.  Journ.  Anat,  1908,  vol.  8,  pp.  251-284),  whose  account  may  be 
summarized  as  follows: 


NOTOCHORD  83 

In  an  embryo  measuring  5.5  mm.  the  notochord  is  a  rod  of  cells  surrounded  by  a 
thin  notochordal  sheath.  A  cross  section  contains  about  eight  wedge-shaped  cells. 
In  an  embryo  measuring  9  mm.  it  is  larger,  and  a  cross  section  shows  about  fifteen 
cells  at  the  periphery,  and  three  or  four  at  the  center.  In  an  embryo  of  n  mm.  the 
cells  have  lost  all  definite  arrangement  and  are  more  or  less  vacuolated.  The  vacuoles 
increase  in  size  and  number,  and  are  found  to  contain  mucin  or  a  gelatinous  mucin- 
like  substance.  In  an  embryo  measuring  17  mm.  the  cell  walls,  which  up  to  this 
time  have  remained  intact,  are  breaking  down  (or  being  absorbed)  and  the  mucin 
escapes  from  the  vacuoles.  The  cells  are  united  by  strands  of  cytoplasm  and  the 
notochordal  tissue  now  resembles  mesenchyma.  The  syncytial  network  continues 
to  enlarge,  both  by  growth,  and  by  the  formation  of  a  greater  number  of  vacuoles. 
In  a  much  older  embryo  (250  mm.)  the  formerly  continuous  peripheral  sheet  of 
syncytial  tissue  is  broken  in  many  places  by  large  masses  of  mucin.  In  the  center 
of  this  accumulation,  the  slender  syncytial  network  seems  suspended  (cf.  Fig.  70). 
In  the  adult  the  syncytium  has  become  divided  into  groups  of  vacuolated  cells 
imbedded  in  a  gelatinous  matrix.  Thus  it  acquires  a  resemblance  to  cartilage  in 
several  particulars,  but  it  should  be  regarded  as  a  distinct  tissue. 

The  human  notochord  undergoes  a  development  similar  to  that  of 
the  pig.  After  it  has  ceased  to  be  an  epithelioid  rod  of  cells,  its  most 
characteristic  condition  is  that  shown  in  Fig.  70,  which  includes  a  portion 
of  the  nucleus  pulposus  from  an  embryo  of  the  fifth  month.  The  noto- 
chordal tissue  forms  a  vacuolated  syncytium  suspended  in  the  gelatinous 
matrix,  which,  at  the  periphery  of  the  nucleus  pulposus,  is  bounded  by  a 
structureless  membrane.  Very  rarely  the  notochord  is  the  source  of 
tumors  which  are  composed  of  tissue  similar  to  that  normally  found 

nucleus  pulposus. 

*— rr 

BONE. 

Bone  develops  relatively  late  in  embryonic  life,  after  the  muscles, 
nerves,  vessels,  and  many  of  the  organs  have  been  formed.  The  skeleton 
at  that  time  consists  of  hyaline  cartilages,  which  are  later  replaced  by 
the  corresponding  bones  of  the  adult.  According  to  Kolliker,  Robert 
Nesbitt  was  the  first  to  point  out  that  the  bones  are  not  indurated  or 
transmuted  cartilages,  but  are  new  formations,  produced  around  the 
cartilages  which  are  later  destroyed.  Moreover,  in  his  "Human  Osteogeny 
Explained  in  Two  Lectures"  (London,  1736),  Nesbitt  showed  that 
certain  bones  develop  directly  from  connective  tissue  without  having 
been  preformed  in  cartilage.  These  are  now  called  membrane  bones  in 
distinction  from  cartilage  bones.  The  membrane  bones  are  the  bones 
of  the  face  and  the  flat  bones  of  the  skull.  They  include  the  interparietal 
or  upper  part  of  the  occipital,  the  squamous  and  tympanic  parts  of  the 
temporal,  the  medial  pterygoid  plate  of  the  sphenoid,  the  parietal,  frontal, 
nasal,  lachrymal,  zygomatic  (malar)  and  palate  bones,  together  with  the 
vomer,  maxilla  and  almost  the  entire  mandible.  Nesbitt  correctly 


84 


HISTOLOGY 


concluded  that  there  is  but  one  method  of  bone  formation,  whether  or 
not  it  takes  place  in  relation  with  cartilage,  but  he  was  unaware  of  the 
existence  of  cells,  and  believed  that  bones  were  produced  from  an  ossifying 
juice  derived  from  the  blood. 

Development  of  bone.  Bone  formation  begins  with  the  production 
of  a  layer  or  spicule  of  matrix  which  stains  red  with  eosin.  As  to  the 
origin  of  this  matrix  there  is  the  same  difference  of  opinion  which  obtains 
in  regard  to  other  intercellular  products.  It  has  been  asserted  that  it 
proceeds  from  osteogenic  fibers,  which  are  modified  white  fibers  of  the 
connective  tissue.  Frequently  a  spicule  of  matrix  is  seen  to  fray  out 
into  the  connective  tissue,  as  shown  in  the  lower  part  of  Fig.  71.  Between 
the  osteogenic  fibers,  calcareous  granules  may  then  be  deposited  until 

Osteoblasts.        Calcifying  connective  tissue  bundles.      Bone  matrix.      Bone  cells. 


^»L_sa.-—        \ — —  "^.,.        \ 

*-^.j»  ^     'Nji"    "***  S 


FIG.  71. — FROM  A  SECTION  OF  THE  MANDIBLE  OF  A  HUMAN  EMBRYO  OF  FOUR  MONTHS.     X  240. 

the  fibers  are  lost  in  a  homogeneous  calcified  matrix.  According  to 
this  opinion  the  matrix  is  essentially  an  intercellular  formation.  Others 
consider  that  the  matrix  is  produced  by  a  transformation  of  the  exoplasm 
of  bone-forming  cells,  or  osteoblasts. 

Osteoblasts  are  derived  from  mesenchymal  or  young  connective 
tissue  cells  through  an  increase  in  their  protoplasm  and  a  shortening  of 
their  processes.  They  are  found  in  contact  with  the  surface  of  spicules 
of  bone,  arranged  in  an  epithelioid  layer  (Fig.  72).  There  is  great  varia- 
tion in  their  shape.  Often  they  are  pyramidal,  but  they  may  rest  upon 
the  bone  either  by  a  broad  base  or  a  pointed  extremity.  Their  round 
nuclei  may  be  in  the  part  of  the  protoplasm  next  to  the  bone,  or  away 
from  it  as  far  as  possible.  Active  osteoblasts  tend  to  be  cuboidal  or 
columnar,  but  as  bone  production  ceases  they  may  become  quite  flat. 
They  form  bone  only  along  that  surface  which  is  applied  to  the  matrix. 
As  the  strand  of  bone  grows  broader  through  their  activity,  it  encloses 
here  and  there  an  osteoblast,  which  thus  becomes  a  bone  cell  (Fig.  72). 
Apparently  bone  cells  do  not  divide,  and  if  they  produce  matrix,  thus 


BONE  85 

becoming  more  widely  separated  from  each  other,  it  is  only  to  a  slight 
extent  and  in  young  bones;  they  are  therefore  quite  inactive.  Each  bone 
cell  occupies  a  space  in  the  matrix,  called  as  in  cartilage,  a  lacuna,  but 
unlike  the  lacunae  of  cartilage  those  in  bone  are  connected  by  numerous 
delicate  canals,  the  canaliculi.  In  ordinary  specimens  the  canaliculi  are 
visible  only  as  they  enter  the  lacunae,  which  are  thus  made  to  appear  stel- 
late. The  matrix  around  the  lacunae  resists  strong  hydrochloric  acid 
which  destroys  the  ordinary  matrix,  and  so  may  be  isolated  in  the  form 
of  "bone  corpuscles."  The  "corpuscles"  correspond  with  the  capsules 
of  cartilage,  which  may  be  isolated  in  the  same  way.  The  bone  cells 
nearly  fill  the  lacunae  and  send  out  very  slender  processes  into  the  canal- 
iculi. These  may  anastomose  with  the  processes  of  neighboring  cells,  as 

Osteoblast  becoming  a  bone  cell.     Bone  cell.    Osteoblast. 

K Uncalcified 

matrix. 


'?- —  Calcified 

matrix. 


FIG.  72. — PART  OF  A  CROSS  SECTION  OF  THE  SHAFT  OF  THE  HUMERUS,  FROM  A  HUMAN  EMBRYO  OF  THE 

FOURTH  MONTH.     X  675. 


can  be  seen  in  the  embryo,  but  it  is  doubtful  if  this  condition  is  retained 
in  the  adult.  The  processes,  moreover,  are  so  fine  that  ordinarily  they  are 
invisible. 

The  spicules  of  bone,  containing  bone  cells  and  beset  with  osteoblasts, 
increase  in  size  and  unite  with  one  another,  so  as  to  form  a  spongy  net- 
work enclosing  areas  of  vascular  connective  tissue.  These  areas  are 
not  entirely  surrounded  by  bone,  but  retain  connections  with  the  exterior, 
through  which  the  vessels  may  enter  and  leave.  It  is  evident  that  if  the 
spicules  continued  to  thicken,  while  new  ones  were  added  at  the  periphery, 
the  bone  would  soon  become  quite  solid  and  heavy.  This  is  prevented 
by  the  destruction  or  resorption  of  certain  spicules,  which  begins  at  a 
very  early  stage.  It  may  be  studied  advantageously  in  the  developing 
mandible  of  a  pig  embryo,  10  cm.  in  length.  At  this  stage  the  teeth 
are  growing  rapidly,  and  around  each  tooth  the  spicules  of  bone  are 
being  destroyed  so  as  to  produce  a  larger  socket;  at  the  same  time  the 
jaw  is  increasing  in  thickness  by  the  formation  of  new  bone  over  its  outer 


86 


HISTOLOGY 


surface.     Toward  the  area  of  resorption  the  osteoblasts  become  flatter 
and  less  numerous,  finally  disappearing. 

In  sections  of  bone,  the  places  where  resorption  is  going  on  may  be 
recognized  by  the  presence  of  large  multinucleate  cells,  which  Kolliker 
in  1873  named  "bone  destroyers"  or  ostoclasts  (preferably  spelled  osteo- 
clasts).  They  are  shapeless  masses  of  protoplasm  without  any  limiting 
membrane,  containing  usually  from  one  to  twenty  nuclei  (Fig.  73).  In 
the  largest  of  them,  Kolliker  counted  from  fifty  to  sixty  nuclei.  He 


•Osteoblasts. 


Haversian  canals  in  the 
process  of  formation. 


Blood  vessels. 
Perichondrial  bone. 


Finished     Haversian 
canal. 


Empty  lacunae. 


Osteoclast. 


Endochondrial  border- 
line. 


Endochondrial  bone. 
FIG.  73. — PORTION  OF  A  CROSS  SECTION  OF  A  TUBULAR  BONE  OF  A  NEWBORN  KITTEN. 

believed  that  they  arose  from  osteoblasts  through  repeated  nuclear  di- 
vision. Apparently  they  are  not  due  to  a  fusion  of  cells;  and  they  have 
nothing  in  common,  except  their  large  size,  with  the  giant  cells  of  the  bone 
marrow,  which  will  be  described  in  connection  with  the  blood.  Osteo- 
clasts  are  found  along  the  surface  of  the  bone,  sometimes  forming  rounded 
elevations  or  caps  at  the  extremities  of  spicules,  and  sometimes  imbedded 
in  shallow  excavations  known  as  Howship's  lacuna.  There  seems  to  be 
no  satisfactory  evidence  that  the  osteoclasts  are  the  active  cause  of  bone 
destruction.  On  the  contrary  they  appear  to  be  degenerating  cells,  pro- 
duced by  those  conditions  which  lead  to  the  dissolution  of  bone. 


BONE  87 

The  processes  of  bone  formation  and  resorption  just  described  take 
place  both  in  membrane  and  in  cartilage  bones.  "  As  the  membrane  bones 
enlarge,  the  central  portion,  through  resorption,  becomes  loose  spongy  bone 
(substnntia  spongiosa),  which  is  enclosed  on  all  sides  by  an  outer  layer  of 
compact  bone  (substantia  compacta).  In  the  flat  bones  of  the  skull  the 
compact  substance  forms  the  outer  and  inner  "tables,"  which  have  the 
spongy  "diploe"  between  them.  The  cartilage  bones  likewise  consist 
of  spongy  and  compact  portions. 


Hyaline 
cartilage. 


Perichondrial 
bone. 


FIG.  74- — A  DORSO-PALMAR  LONGITUDINAL  SECTION  OF  A  PHALANX  OF  THE  LITTLE  FINGER,  FROM  A  HUMAN 
EMBRYO  OF  THE  SIXTH  MONTH.     X  60. 


Replacement  of  the  skeletal  cartilages.  The  changes  within  the  skeletal 
cartilages  during  the  formation  of  bone  may.  be  studied  advantageously 
in  longitudinal  sections  of  any  developing  "long  bone,"  or  in  transverse 
sections  of  the  vertebrae  from  pig  embryos  measuring  about  10  cm.  The 
vertebrae  exhibit  several  processes  which  will  be  cut  lengthwise  in  trans- 
verse sections.  Fig.  74  represents  a  longitudinal  section  of  a  phalanx 


88 


HISTOLOGY 


around  which  ossification  has  begun.  On  either  side  of  the  shaft  of 
hyaline  cartilage,  the  matrix  of  which  stains  blue  with  haematoxylin, 
there  is  a  strip  of  bone,  the  matrix  of  which  is  stained  red  with  eosin. 
These  strips  are  sections  of  a  band  of  bone  which  completely  encircles 
the  middle  part  of  the  cartilage.  It  has  been  formed  by  osteoblasts  which 
developed  in  the  perichondrium.  The  portion  of  the  cartilage  which  is 
surrounded  by  bone  has  begun  to  degenerate.  Its  capsules  have  been 


Enlarged 

cartilage 

cells. 


Perichondrial 
bone. 


Periosteum: 


FlG.     75. A    DORSO-PALMAR    LONGITUDINAL    SECTION    OF    A    MlDDLE-FINGER    PHALANX, 

FROM  A  HUMAN  EMBRYO  OF  THE  FOURTH  MONTH.     X  60. 

resorbed,  and  the  enlarged  lacunae  are  beginning  to  coalesce.  The  matrix 
of  the  cartilage  in  this  region  takes  a  deeper  stain,  and  calcareous  granules 
are  being  deposited  within  it. 

On  the  left  of  Fig.  74,  a  bud  of  perichondrial  tissue  is  seen  entering 
the  shaft  of  the  cartilage,  and  similar  buds  may  invade  it  from  other 
sides.  Within  the  cartilage  the  ingrowing  perichondrial  tissue  forms  the 
primary  marrow,  which  is  a  very  vascular  connective  tissue.  As  it  ad- 
vances, the  walls  of  the  lacunae  are  resorbed,  setting  free  the  cartilage 
cells.  Formerly  it  was  thought  that  these  cartilages  cells  became  osteo- 
blasts, but  they  are  now  considered  to  be  dying  cells,  without  further 
function. 


BONE 


89 


Meanwhile  the  cartilage  continues  to  grow,  especially  in  length. 
This  is  brought  about  by  successive  transverse  divisions  of  the  cells  of  the 
shaft,  so  that  they  become  arranged  in  more  or  less  definite  longitudinal 
rows  (Fig.  75).  The  thin  transverse  walls  of  the  lacunae  in  these  rows  are 


Osteogenic 
tissue. 


if  Hyaline  carti- 
;>  lage  (cells  in 
:l  groups). 


Hyaline'f  car- 
tilage, (cells 
enlarged) . 


Periosteum.      /      Perichondrial 

Osteoblasts.  .   Osteoblasts. 


Calcified 
matrix 
of  hya- 
line car- 
tilage. 


Endochondrial  bone. 
Osteoclasts. 

Marrow 

cells. 

FIG.  76. — FROM  A  LONGITUDINAL  SECTION  OF  THE  PHALANX  OF  THE  FIRST  FINGER  OF  A  HUMAN  EMBRYO  OF 

THE  FOURTH  MONTH.     X  220. 

dissolved  more  readily  than  the  thicker  longitudinal  walls,  and  the  deep- 
blue  ragged  spicules  of  calcined  matrix  which  are  thus  produced,  are  there- 
fore generally  elongated.  Osteoblasts,  derived  from  the  primary  marrow, 
arrange  themselves  on  these  spicules,  and  form  bone  in  the  same  manner 


9o 


HISTOLOGY 


as  elsewhere.     Thus  the  spicules  of  calcified  matrix,  staining  blue,  become 
encased  in  the  matrix  of  bone  which  stains  red  (Figs.  75  and  76). 

From  what  has  been  said,  it  is  clear  that  bone  is  formed  both  around 
the  cartilage  (perichondrial  bone)  and  within  the  cartilage  (endochon- 
drial  bone).  In  long  bones  and  flat  bones,  ossification  is  at  first  perichon- 
drial and  later  endochondrial;  in  short  bones  it  is  endochondrial  until 
the  cartilage  has  been  entirely  replaced.  Thus  the  part  taken  by  endo- 
chondrial and  perichondrial  ossification  varies  greatly  in  different  bones. 
As  the  bone  grows,  the  older  parts  which  have  formed  in  relation  with 


Haversian 
Periosteum.          depressions. 

l 


Endochondrial     Perichondrial 
bone.  bone. 


Remains  of  calci 

fied  matrix  of 

cartilage. 


FIG.  77. — FROM  A  CROSS  SECTION  OF  THE  SHAFT  OF  THE  HUMERUS,  FROM  A  HUMAN  EMBRYO  OF  THE  FOURTH 

MONTH.     X  80. 

the  cartilage  are  resorbed.  In  the  shaft  of  the  humerus  from  a  human 
embryo  of  the  fourth  month  (Fig.  77),  only  a  thin  and  interrupted  layer 
of  calcified  cartilage  remains  to  mark  the  boundary  between  perichondrial 
and  endochondrial  bone,  and  in  the  adult  all  traces  of  this  layer  have  dis- 
appeared. This  is  true  of  most  bones,  but  in  the  auditory  ossicles  cal- 
cified cartilage  is  found  throughout  life. 

The  final  stages  in  the  replacement  of  the  cartilages  by  bone  take 
place  long  after  birth,  when  the  bones  have  increased  greatly  in  diameter 
and  length.  The  growth  in  diameter  is  accomplished  by  the  deposition 
of(  new  layers  externally,  and  the  enlargement  of  the  marrow  cavity, 


BONE 


I 


through  resorption,  internally.  This  explains  why  a  band  of  metal  placed 
around  the  bone  of  a  young  animal  is  later  found  within  the  marrow. 
The  internal  resorption  takes  place  in  such  a  way  that  a  meshwork  of 
spicules  and  plates,  denser  toward  the  periphery,  remains  within  the  shaft, 
and  the  marrow  occupies  its  interstices.  To  a  limited  extent  new  bone  is 
formed  in  the  interior  of  the  shaft  by  osteoblasts  in  its  lining  membrane, 
called  the  endosteum.  The  deposition  of  new  layers  externally  is  produced 
by  osteoblasts  in  the  periosteum,  which  is  a  specialized  connective  tissue 
layer  surrounding  the  bone.  It  replaces,  and  apparently  is  derived  from, 
the  perichondrium  of  the  original  cartilage.  The  extent  to  which  new 
bone  is  formed,  and  its  distribution,  may 
be  determined  by  feeding  madder  to  grow- 
ing animals.  This  dye,  as  has  long  been 
known,  imparts  a  red  color  to  the  matrix 
of  bone  deposited  while  it  forms  a  part  of 
the  diet.  By  this  means  Kolliker  deter- 
mined that  the  deposition  of  periosteal 
bone  is  not  uniform.  In  a  given  bone, 
there  will  be  unstained  areas,  where  no 
new  bone  is  being  formed,  or  where  an  ex- 
ternal resorption  is  taking  place.  In  this 
way  the  bones  acquire  their  characteristic 
modelling. 

Growth  in  length  occurs  chiefly  through 
the  activity  of  the  uncalcified  cartilage. 
In  a  long  bone,  ossification  first  produces  a 

band  of  bone  encircling  the  cartilage,  and  then  a  hollow  shaft  of  bone 
with  a  rounded  mass  of  cartilage  at  either  end  (Fig.  78,  A,  B).  The  cells  in 
these  masses  continue  to  divide,  prolonging  the  longitudinal  rows  of  cells 
such  as  are  seen  in  Fig.  75.  As  ossification  takes  place  at  one  end  of  these 
rows,  new  cells  are  formed  at  the  other,  and  thus  the  length  of  the  shaft  or 
diaphysis  increases.  Certain  bones  have  been  found  to  grow  more  at  one 
end  than  at  the  other.  After  a  time  osteogenic  tissue  invades  the  cartilages 
at  the  extremities  of  the  bone,  extending  into  them  from  the  marrow 
cavity  of  the  shaft.  It  forms  a  small  bone  within  each,  and  these  are 
known  as  epiphyses  (Fig.  78,  D).  Between  the  epiphysis  and  the  diaphy- 
sis there  remains  a  layer  of  cartilage,  called  the  epiphyseal  synchondrosis, 
which  allows  further  growth  in  length.  The  cells  which  it  produces  are 
added  chiefly  to  the  shaft.  The  relation  of  the  epiphyses  to  the  growth 
of  bone  was  demonstrated  by  early  experiments,  in  which  metal  pegs 
were  placed  in  the  bones  of  young  animals.  Pegs  in  the  shaft  scarcely 
separate  from  one  another  during  growth,  but  a  peg  in  the  epiphysis 
moves  away  from  one  in  the  diaphysis.  The  epiphyses  are  formed  at 


FIG.  78. — PLAN  OF  OSSIFICATION  IN  A 
LONG  BONE,  BASED  UPON  THE  TIBIA. 

Cartilage  is  drawn  in  black,  and  bone  is 
stippled.  art.,  Articular  cartilage; 
ep.,  epiphysis;  diaph.,  diaphysis. 


92  HISTOLOGY 

various  times  after  birth,  or,  in  the  tibia,  shortly  before  birth;  they  unite 
with  the  diaphyses  usually  between  the  eighteenth  and  twenty-second 
years,  when  the  bones  have  acquired  their  full  length.  At  that  time  noth- 
ing is  left  of  the  original  cartilage  except  the  layer  of  articular  cartilage 
which  covers  the  joint  surfaces.  Details  in  regard  to  the  time  when 
ossification  begins  in  the  various  bones,  the  number  of  centers  involved 
(for  many  bones  have  more  than  the  three  which  have  here  been  de- 
scribed), and  the  time  when  these  join  the  main  bone,  will  be  found  in  text- 
books of  anatomy,  and,  together  with  many  references  to  important 
studies  of  bone  development,  in  Bidder's  "Osteobiologie"  (Arch.  f.  mikr. 
Anat.,  1906,  vol.  68,  pp.  137-213). 

Structure  of  Bone  in  the  Adult.  The  properties  of  adult  bone  are  essen- 
tially those  of  its  matrix,  which  consists  of  organic  and  inorganic  constitu- 
ents intimately  blended,  and  perhaps  chemically  combined.  Of  the  in- 
organic matter,  over  80%  is  calcium  phosphate,  Cas  (PO^;  the  remainder 
includes  chlorides,  carbonates,  fluorides  and  sulphates  of  calcium,  sodium, 
potassium  and  magnesium.  In  order  to  cut  sections  of  bone,  this  in- 
organic matter  must  be  removed,  and  decalcification  is  usually  accom- 
plished by  placing  the  specimen,  after  it  has  been  preserved,  in  dilute  nitric 
acid  (3-5%)  for  several  days  or  weeks.  The  matrix  then  has  the  con- 
sistency of  cartilage.  Its  organic  portion,  which  remains,  is  composed 
chiefly  of  collagen,  together  with  osseo-mucoid.  The  collagen  occurs  in 
very  fine  white  fibrils  which  are  gathered  in  bundles,  arranged  in  thin 
layers  or  lamella.  Within  these  layers  the  fibers  occur  in  parallel  sets 
which  tend  to  cross  one  another  at  right  angles,  thus  producing  a  lattice 
work.  These  " decussating  fibers"  are  seen  only  in  special  preparations 
in  which  a  lamella  has  been  peeled  off,  so  that  it  can  be  examined  in  sur- 
face view.  The  calcareous  matter  is  said  to  be  deposited  in  the  cement 
substance  between  the  fibers,  and  not  within  them.  Coarser  uncalcified 
fibers  are  found  in  embryonic  bone  and  in  certain  situations  in  adult  bone 
—for  example,  at  the  sutures  and  the  places  where  tendons  are  inserted. 
They  also  extend  into  the  bone  from  the  periosteum  (Fig.  79),  constitut- 
ing the  "perforating  fibers"  (Sharpey's  fibers).  The  perforating  fibers  of 
the  bones  of  the  skull  are  entirely  collagenous.  These  bones  in  the  adult, 
together  with  the  entire  skeleton  at  birth,  contain  no  elastic  fibers;  but  in 
other  bones  of  the  adult  elastic  fibers  accompany  the  perforating  fibers 
(Schulz,  Anat.  Hefte,  Abt.  i,  1896,  vol.  6,  pp.  117-153). 

The  periosteum  consists  of  two  layers.  It  has  an  outer  layer  of  dense 
connective  tissue,  rich  in  blood  vessels  and  containing  also  lymphatic 
vessels  and  nerves.  It  blends  with  the  surrounding  looser  connective 
tissue  and  in  places  with  fasciae  and  tendons.  The  inner  layer  has  few 
vessels  but  contains  an  abundance  of  elastic  fibers.  They  are  chiefly 
parallel  with  the  long  axis  of  the  bone,  but  in  the  periosteum  of  the  bones 


BONE  93 

of  the  roof  of  the  skull  they  form  an  interlacing  network  (Schulz).  Perfo- 
rating fibers,  such  as  were  described  in  the  preceding  paragraph,  may 
arise  from  this  layer;  and  others,  both  white  and  elastic,  derived  from  ten- 
dons, may  pass  through  it  into  the  bone.  In  this  way  the  tendons  acquire 
a  very  firm  insertion.  The  cells  of  the  inner  layer  of  the  periosteum  are 
spindle-shaped  or  flattened  connective  tissue  cells,  together  with  the  more 
cuboidal  osteoblasts  which  rest  against  the  bone.  In  young  bones  these 
are  so  numerous  as  to  form  a  third  layer  of  the  periosteum.  In  the 
adult  they  are  few  in  number,  but  are  capable  of  proliferation,  and  to- 
gether with  those  in  the  endosteum.  they  are  the  source  of  new  bone  after 
injury.  The  periosteum,  in  bodies  which  have  been  kept  a  week  at  15° 
C.,  is  said  to  be  capable  of  producing  bone  when  transplanted  to  another 
body;  and  after  operations  in  which  a  shaft  of  'bone  has  been  shelled 
out  from  its  periosteum,  a  new  shaft  may  be  formed. 

Beneath  the  periosteum,  as  seen  in  the  cross  section  of  the  shaft  of  a 
long  bone  (Fig.  80) ,  there  are  layers  or  lamellae  of  bone  which  are  parallel 

Periosteum.  Suture.         Perforating  fibers.        Periosteal  lamellae. 

\  ! 


\  i  t 

Blood  vessel.  Volkmann's  canal.       Haversian  canal. 

FIG.  79. — SECTION  ACROSS  A  SUTURE  IN  THE  SKULL  OF  AN  ADULT. 
Prepared  by  Bielschowsky's  method.     X  80. 

with  the  surface.  These  are  the  "outer  ground  lamellae"  or  periosteal 
lamella.  They  are  traversed  by  Sharpey's  perforating  fibers  and  by  small 
blood  vessels  lodged  in  the  so-called  Volkmann's  canals.  The  bone 
cells  occupy  lacunae,  situated  between  the  lamellae,  and  in  Fig.  80  they 
.are  seen  as  small  spots.  In  the  lowest  part  of  the  figure,  a  portion  of 
the  marrow  has  been  included.  The  marrow  is  surrounded  by  the 
endosteum,  external  to  which  are  the  "inner  ground  lamellae"  or  endosteal 
lamella.  These  are  parallel  with  the  inner  surface  of  the  bone. 

Between  the  periosteal  and  the  endosteal  lamellae  there  is  a  dense 
mass  of  matrix  unlike  anything  found  in  embryonic  bone.  Scattered 
through  it,  numerous  blood  vessels  are  seen  in  cross  section.  Each 
vessel  is  surrounded  by  concentric  lamella  which  present  a  very  charac- 


94 


HISTOLOGY 


teristic  figure.  Such  vessels  are  said  to  occupy  Haversian  canals  (named 
for  the  English  anatomist,  Clopton  Havers).  Volkmann's  canals  contain 
vessels,  but  they  are  not  surrounded  by  concentric  lamellae.  An  Haver- 
sian canal  often  contains  two  vessels,  an  artery  and  a  vein,  together 
with  a  small  amount  of  connective  tissue  and  occasional  fat  cells;  flattened 
osteoblasts  may  rest  against  the  surrounding  bone,  and  send  processes 
into  it.  The  concentric  lamellae  enclosing  an  Haversian  canal  constitute 


Resorption  line. 


Volkmann's  canals. 


Periosteum. 


^^  Periosteal  lamellae. 
|L-"-'  Perforating  fibers. 


_!:_  ___  Haversian  lamellae. 
-•—  -----  Haversian  canal. 


Interstitial  lamellae. 


_  Endosteal  lamellae. 


I— .  Marrow. 


FIG.  80.— PART  OF  A  CROSS  SECTION  OF  A  DECALCIFIED  PHALANX  FROM  AN  ADULT. 


an  Haversian  system.     Interstitial  lamella,  irregularly  arranged,  fill  the 
intervals  between  the  Haversian  systems. 

The  way  in  which  the  compact  bone  of  the  adult  is  formed  from  the 
trabecular  network  of  the  embryo  is  indicated  in  the  diagram,  Fig.  81 
(cf.  also  Fig.  73).  After  an  area  of  vascular  tissue  has  been  surrounded 
by  bone,  the  osteoblasts  form  lamellae,  gradually  closing  in  from  all 
sides  until  only  a  slender  canal  remains.  Successive  stages  are  shown 
in  Fig.  81,  B. -V.,  H.  C1,  and  H.  C2,  respectively.  The  deposition  of  the 
concentric  lamellae  is  not  continuous.  It  is  interrupted  by  periods  of 


BONE 


95 


FIG.  81. — DIAGRAM  OF  THE  DEVELOPMENT  OF  BONE. 

(In  part,  after  Duval.) 

f.,  Fibrous  layer  of  periosteum;  o.,  osteogenic  layer  of  peri- 
osteum; os.,  osteoblast;  b.c.,  bone  cell;  B.  V.,  blood  vessel; 
H.  C1.,  beginning  Haversian  canal;  H.  C2.,  complete 
Haversian  canal;  i.  1.,  interstitial  lamellae,  c.  1.,  concen- 
tric lamellae;  Sh.,  Sharpey's  perforating  fibers. 


resorption,  after  which  the  deposition  of  bone  is  resumed.     Resorption 
lines  are  frequently  seen  in  the  Haversian  systems  (Fig.  80). 

Longitudinal  sections  of 
decalcified  bone  show  the  way 
in  which  the  Haversian  canals 
connect  with  one  another 
(Fig.  82).  The  lamellae  are 
not  so  strikingly  subdivided 
into  the  groups  seen  in  cross 
sections,  since  both  the  con- 
centric lamellae  and  the 
ground  lamellae  are  longitudi- 
nal layers.  The  lacunae  of 
the  Haversian  systems,  how- 
ever, are  flattened,  parallel 
with  the  course  of  the  Haver- 
sian canals,  whereas  those  of 
the  interstitial  lamellae  are 
more  rounded  or  stellate. 
The  Haversian  lacunae  have  been  described  as  shaped  like  melon  seeds. 
Certain  features  of  bone  which  can  scarcely  be  seen  in  decalcified 

specimens  are  rendered 
conspicuous  in  layers  of 
dried  bone,  ground  upon 
an  emery  wheel  until 
thin  enough  to  be  trans- 
lucent. The  Haversian 
canals  and  lacunae  with 
the  canaliculi  projecting 
from  them,  are  then 
empty,  except  for  air 
and  particles  of  bone 
dust.  The  specimens 
are  mounted  in  thick 
balsam,  which  spreads 

Fat  drops.  OV6r    the    bone    without 

filling  the  lacunae  and 
canaliculi.  When  seen 
under  the  microscope 
these  structures  appear 
black  (Fig.  83),  the  air 
within  them  being  highly  refractive.  In  such  preparations  the  way  in 
which  the  canaliculi  pass  from  one  lacuna  to  another,  their  connections 


Periosteum. 


FIG.    82. — FROM  A  LONGITUDINAL   SECTION   OF  A  HUMAN  META- 

CARPAL.       X    30. 

Fat  drops  are  seen  in  the  Haversian  canals.     At  x  Haversian  canals 
open  on  the  outer,  and  at  xx  on  the  inner  surface  of  the  bone. 


96 


HISTOLOGY 


with  the  Haversian  canal,  and  their  manner  of  branching  may  be  readily 
observed.  Although  these  canals  are  all  present  in  the  decalcified  bone, 
they  are  usually  inconspicuous  and  often  invisible.  It  has  been  impossi- 
ble to  determine  absolutely  whether  the  bone-cells  anastomose  with  one 
another  through  these  canals,  but  it  is  considered  probable  that  their 
processes  do  not  extend  very  far  into  them. 

Vessels  and  Nerves  in  Bone.     The  blood  vessels  of  the  marrow,  bone 
and  periosteum  freely  connect  with  one  another.     Small  branches  from 

the  arteries  and  veins  of  the  peri- 
osteum enter  the  bone  everywhere, 
through  the  Volkmann's  and  Ha- 
versian canals,  and  anastomose 
with  the  vessels  in  the  marrow. 
The  marrow  receives  its  blood 
from  the  nutrient  artery,  which 
gives  off  branches  on  its  way 
through  the  compact  bone  and 
forms  a  rich  vascular  network  in 
the  marrow.  Of  the  larger  veins 
which  drain  this  network,  one 
passes  out  beside  the  nutrient 
artery  and  others  connect  freely 
with  the  vessels  in  the  compact 
bone.  Lymphatic  vessels  are  found 
only  in  the  outer  layer  of  the 
periosteum.  Numerous  medul- 
lated  and  non-medullated  nerves 
are  present  in  the  periosteum, 
where  some  of  them  end  in  lamellar 

corpuscles.  Others  enter  the  Haversian  canals  and  marrow,  chiefly  to 
innervate  the  vessels.  The  nerves  will  be  described  in  a  later  chapter. 


FIG.  83. — CROSS  SECTION  OF  COMPACT  BONE,  FROM 
THE  SHAFT  OF  THE  HUMERUS,  SHOWING  THREE 
HAVERSIAN  SYSTEMS  AND  PART  OF  A  FOURTH  . 
(Sharpey.) 


THE  JOINTS. 

Bones  may  be  joined  in  two  ways,  either  by  a  synarthrosis  which 
ajlows  little  or  no  motion  between  them,  or  by  a  diarthrosis  which  permits 
them  to  move  freely  upon  one  another. 

In  a  synarthrosis  the  mesenchymal  tissue  between  the  adjacent  bones 
may  form  dense  connective  tissue,  such  as  passes  from  one  bone  to  an- 
other across  the  sutures  of  the  skull  (Fig.  79);  or  it  may  form  cartilage, 
in  which  case  the  joint  is  known  as  a  synchondrosis.  The  cartilage  may 
be  hyaline,  as  in  the  epiphyseal  synchqndroses,  but  often  it  is  fibrous,  as 
in  the  intervertebral  synchondroses. 


JOINTS 


97 


In  a  diarthrosis  the  connective  tissue  between  the  bones  remains  com- 
paratively loose  in  texture,  and  a  cleft  forms  within  it,  containing  tissue 
fluid.  This  is  the  joint  cavity  (Fig.  84).  It  is  bounded  in  part  by  flat- 
tened connective  tissue  cells,  which  spread  out  and  form  an  imperfect 
epithelium  (Fig.  85).  This  is  not  a  continuous  layer  of  cells,  since  in 
many  places  the  fibrous  tissue  comes  to  the  surface.  The  connective 
tissue  layer  blends  with  the  perichondrium,  which  in  turn  passes  into 
cartilage,  and  a  portion  of  the  cartilage,  uncovered  by  perichondrium, 
helps  to  bound  the  joint  cavity. 


FIG.  84. — PHALANGEAL  JOINT 
FROM  A  HUMAN  EMBRYO  OF 
THE  FOURTH  MONTH. 

car.,  Cartilage;  j.  c.,  joint  cavity; 
s.  f.,  stratum  fibrosum;  s.  s., 

stratum  synoviale. 


FIG.  85. — AN  ENLARGED  DRAWING  OF  THE  LEFT  PART  OF  THE  JOINT 

SHOWN  IN  FIG.  84. 

b.  v.,  Blood  vessel;  car.,  cartilage;   j.  c.,   joint  cavity;    mes.  epi., 
mesenchymal  epithelium. 


The  articular  cartilages  are  sometimes  fibrous  (as  noted  on  p.  81)  but 
usually  they  are  hyaline.  They  vary  in  thickness  from  0.2  mm.  to  5  mm., 
being  thinner  at  the  periphery.  The  cells  near  the  free  surface  are  flat- 
tened. In  the  middle  strata  they  are  rounded  and  are  often  arranged  in 
groups;  in  the  deepest  layers  they  tend  to  be  in  rows  perpendicular  to 
the  surface.  The  matrix  becomes  calcified  as  the  cartilage  connects 
with  the  bone,  and  a  line  of  demarcation  separates  the  calcified  from  the 
uncalcified  portion  (Fig.  86).  In  the  uncalcified  cartilage,  cells  with 
processes  extending  into  the  adjacent  matrix  have  been  described,  and 
the  deeper  layers  of  flattened  cells  may  exhibit  lobed  nuclei. 

The  joint  capsule  consists  of  an  outer  layer  of  dense  connective  tissue, 
the  stratum  fibrosum;  and  an  inner  loose  layer  of  which  the  mesenchymal 
epithelium  is  a  part,  the  stratum  synoviale  (Fig.  84).  The  fibrous  layer 
is  specially  thickened  in  various  places  to  form  the  ligaments  of  the  joint. 

7* 


98 


HISTOLOGY 


It  may  cover  the  end  of  the  bone,  coming  between  it  and  the  joint  cavity; 
thus  the  distal  articular  surface  of  the  radius  is  covered  with  dense  fibrous 
tissue.  In  other  joints,  as  in  the  shoulder  and  hip,  such  tissue  forms  a 
rim,  deepening  the  socket  of  the  joint.  These  rims  are  called  labra 
glenoidalia.  Large  folds  or  plates  of  dense  fibrous  tissue  may  project 
into  the  joint,  covered  by  the  synovial  layer,  thus  forming  the  menisci 
of  the  knee  joint,  and  the  articular  discs  such  as  are  interposed  in  the  stern o- 
clavicular  and  mandibular  joints.  Nerves  and  vessels  are  absent  from 
the  articular  cartilages  of  the  adult,  and  also  from  the  labra  and  articular 
discs. 


Hyaline 
cartilage. 


Calcified 
cartilage. 


iLj«i^>i;'^^~ Bone. 


Marrow 
(fat  cells). 

Blood  vessel. 


FIG.  86. — VERTICAL  SECTION  THROUGH  THE 
HEAD  OF  A  METACARPAL  OF  AN  ADULT  MAN. 
X  so. 


esr 


FIG.  87. — SYNOVIAL  VILLI  WITH 
BLOOD  VESSELS  FROM  A  HUMAN 
KNEE  JOINT.  X  50. 

The  epithelium  has  fallen  from  the 
apex  of  the  left  yillus,  exposing 
the  connective  tissue. 


The  synovial  layer  consists  of  loose  connective  tissue,  generally  with 
abundant  elastic  elements.  In  many  places  it  contains  considerable 
quantities  of  fat.  It  has  nerves  which  may  terminate  in  lamellar  cor- 
puscles, numerous  blood  vessels,  and  lymphatic  vessels  which  may  extend 
close  to  the  epithelium.  The  " epithelium"  is  a  smooth  glossy  layer  of 
connective  tissue  with  parallel  fibers  and  small  round  or  stellate  cells 
containing  large  nuclei.  The  cells  are  sometimes  infrequent,  as  in  places 
where  there  is  unusual  pressure.  Elsewhere  they  may  be  spread  in  a 
single  thin  layer,  or  heaped  together,  making  an  epithelium  of  three  or 
four  strata.  The  synovial  membrane  may  be  thrown  into  coarse  folds 
(plica)  or  into  slender  almost  miser oscopic  projections  (mlli).  The  latter 
impart  a  velvety  appearance  to  the  membrane  on  which  they  occur. 


JOINTS 


99 


On  microscopic  examination  the  synovial  villi  are  seen  to  vary  greatly 
in  shape.  They  are  covered  by  a  simple  or  double  layer  of  synovial 
epithelium,  and  usually,  but  not  invariably,  they  contain  vessels.  The 
synovia  (synovial  fluid)  consists  chiefly  of  water  (94%),  the  remainder 
including  salts,  albumin,  mucoid  substances,  fat  droplets  and  fragments 
of  cells  shed  from  the  membrane. 


f  Enamel. 7- 


Dentine. 


Crown. 


TEETH. 

A  tooth  consists  of  three  parts,  crown,  neck,  and  root  or  roots.  The 
crown  is  that  portion  which  projects  above  the  gums;  the  root  is  the  part 
inserted  into  the  alveolus  or  socket  in 
the  bone  of  the  jaw;  and  the  neck, 
which  is  covered  by  the  gums,  is  the 
connecting  portion  between  the  root 
and  crown.  A  tooth  contains  a  dental 
cavity  filled  with  pulp.  The  cavity  is 
prolonged  through  the  canal  of  the 
root  to  the  apex  of  the  root,  where  it 
opens  to  the  exterior  of  the  tooth  at 
the  foramen  apicis  dentis.  The  fora- 
men is  shown,  but  is  not  labelled,  in 
Fig.  88.  The  solid  portion  of  the 
tooth  consists  of  three  calcified  sub- 
stances, the  dentine  or  ivory  (sub- 
stantia  eburnea),  the  enamel  (sub- 
stantia  adamantina),  and  the  cement 
(substantia  ossea) .  Of  these  the  den- 
tine is  the  most  abundant.  It  forms 
a  broad  layer  around  the  dental  cav- 
ity and  root  cana],  and  is  interrupted 
only  at  the  foramen.  Nowhere  does 
the  dentine  reach  the  outer  surface 
of  the  tooth.  In  the  root  it  is  covered 
by  the  cement  layer,  which  increases 
in  thickness  from  the  neck  toward 
the  apex;  and  in  the  crown  it  is  en- 
closed by  the  broad  layer  of  enamel.  The  enamel,  however,  becomes 
thin  toward  the  neck,  where  it  meets  and  is  sometimes  overlapped  by  the 
cement.  The  pulp,  dentine,  and  cement  are  of  mesenchymal  origin,  the 
dentine  and  cement  being  varieties  of  bone.  The  enamel  is  an  ectodermal 
formation,  but  so  intimately  associated  with  the  others  that  it  may  be 
described  with  them. 


Cement.  — 


FIG.  88. — LONGITUDINAL  GROUND  SECTION  OF  A 
HUMAN  INCISOR  TOOTH.     X  4. 


IOO 


HISTOLOGY 


The  Development  of  the  Teeth.  The  first  indication  of  tooth  develop- 
ment in  human  embryos  is  a  thickening  of  the  oral  epithelium,  which 
has  been  observed  in  specimens  measuring  11-12  mm.  At  this  stage 
the  oral  plate,  which  marks  the  boundary  between  ectoderm  and  ento- 
derm,  has  wholly  disappeared,  but  it  is  evident  that  the  thickening  takes 
place  in  ectodermal  territory.  The  tongue  is  well  developed,  but  the 
upper  and  lower  lips  are  not  as  yet  separated  by  depressions  from  the 
structures  within  the  mouth.  *  Soon  after  the  thickening  has  appeared,  it 
grows  upward  in  the  upper  jaw,  and  downward  in  the  lower  jaw,  into  the 
adjacent  mesenchyma,  thus  forming  an  epithelial  plate  which  follows  the 
circumference  of  either  jaw.  It  undergoes  the  same  sort  of  transformation 
in  both  the  maxilla  and  mandible,  and  the  following  description  of  the 
conditions  in  the  mandible  is  therefore  applicable  to  both.  As  the  plate 
descends  into  the  mesenchyma,  it  divides  into  a  labial  lamina  in  front, 


a         b        c  d 

FIG.  89. — SAGITTAL  SECTION  THROUGH  THE  TONGUE  AND  LOWER  JAW  OF  A  HUMAN  EMBRYO  OF  22   MM. 

X  20. 
a,  Labial  lamina;  b,  dental  lamina;  c,  Meckel's  cartilage;  d,  tongue. 

which  brings  about  the  separation  of  the  lip  from  the  gum,  and  a  dental 
lamina  behind,  which  is  concerned  with  the  production  of  the  teeth  (Fig. 
89).  At  first  the  dental  lamina  is  inclined  decidedly  inward  or  toward 
the  tongue,  as  seen  in  the  figure,  but  later  it  descends  from  the  oral  epithe- 
lium almost  vertically.  -Taken  as  a  whole  it  is  a  crescentic  plate  of  cells 
following  the  line  of  the  gums,  along  which  the  teeth  will  later  appear. 

The  further  development  of  the  dental  lamina  is  shown  diagrammaticr 
ally  in  Fig.  90,  A-D,  each  drawing  representing  a  part  of  the  oral  epithe- 
lium above  and  dental  lamina  below,  freed  from  the  surrounding  mesen- 
chyma. The  labial  side  is  toward  the  left  and  the  lingual  side  toward 
the  right.  Almost  as  soon  as  the  dental  lamina  has  formed,  it  produces  a 
series  of  inverted  cup-shaped  enlargements  along  its  labial  surface  (Fig. 
90,  B),  and  these  become  the  enamel  organs.  There  is  a  separate  enamel 
organ  for  each  of  the  ten  deciduous  teeth  in  either  jaw,  and  they  are  all 
present  in  embryos  of  two  and  one-half  months  (40  mm.).  They  not 


TEETH 


101 


only  produce  the  enamel  but  extend  over  the  roots,  so  that  they' are  de- 
scribed as  forming  moulds  for  the  teeth  which  develop  within  their  con- 
cavities. The  tissue  enclosed  by  the  enamel  organ  is  a  dense  mesen- 
chyma,  constituting  the  dental  papilla.  It  becomes  the  pulp  of  the  tooth, 
and  produces,  at  its  periphery,  the  layer  of  dentine.  As  the  tooth  de- 
velops, the  connection  between  its  enamel  organ  and  the  dental  lamina 


Oral  epithelium. 


Enamel 
organs. 


Dental 
groove 


Dental  lamina. 

Papillae.  Enamel  organs.        Necks  of  enamel  organs. 

ABC  D 

FIG.  90. — DIAGRAMS  SHOWING  THE  EARLY  DEVELOPMENT  OF  THREE  TEETH. 
(One  of  the  teeth  is  shown  in  verticle  section.) 


becomes  reduced  to  a  flattened  strand  or  neck  of  epithelial  tissue,  which 
subsequently  disintegrates. 

In  order  to  produce  enamel  organs  for  the  three  permanent  molars, 
which  develop  behind  the  temporary  teeth  on  either  side  of  the  jaws,  the 
dental  lamina  grows  .backward,  free  from  the  oral  epithelium.  This 
backward  extension  becomes  thickened  and  then  inpocketed  by  a  papilla* 
thus  forming  the  enamel  organ  for  the  first 
permanent  molar  in  embryos  of  17  weeks  (180 
mm.).  It  grows  further  back,  and  gives  rise  to 
the  enamel  organ  for  the  second  molar  at  about 
six  months  after  birth,  and  for  the  third  or  late 
molar  (wisdom  tooth)  at  five  years.  In  rare 
cases,  several  of  which  have  been  reported, 
there  is  a  fourth  molar  behind  the  wisdom  tooth, 
and  it  is  assumed  that  in  these  cases  the  dental 
lamina  continued  its  backward  growth  beyond 
the  normal  limits  (Wilson,  Journ.  Anat.  and 
Physiol.,  1905,  vol.  39,  pp.  119-134). 

The  permanent  front  teeth  develop  from  enamel  organs  on  the  labial 
side  of  the  deep  portion  of  the  dental  lamina  (Fig.  91).  Owing  to  the 
obliquity  of  the  lamina  the  permanent  teeth  are  on  the  lingual  side  of  the 
deciduous  teeth.  The  enamel  organs  for  the  incisors  develop  slightly  in 
advance  of  those  for  the  canines,  but  all  of  these  are  indicated  in  an  embryo 
of  24  weeks  (30  cm.)  described  by  Rose.  He  found  the  enamel  organs 
for  the  first  premolars  in  an  embryo  of  29  weeks  (36  cm.)  and  for  the  second 


QE. 


D.R. 


E.O. 


FIG.  91. — TEETH  FROM  A  HUMAN 
EMBRYO  OF  30  CM.  (Modified 
from  Rose.) 

E.  and  E.  O.f  Enamel  organs  of 
a  deciduous  and  of  a  perma- 
nent tooth  respectively;  D. 
R.j  dental  lamina;  O.  E.,  oral 
epithelium;  P.,  papilla. 


105  HISTOLOGY 

premolars  at  33  weeks  (40  cm.).  Each  front  tooth  develops  in  the  alve- 
olus occupied  by  the  corresponding  deciduous  tooth,  but  later  a  bony 
septum  forms  between  the  two  teeth  and  subdivides  the  alveolus.  When 
the  deciduous  teeth  are  shed,  the  partitions  are  resorbed,  together  with 
the  dentine  and  cement  of  the  roots  of  the  deciduous  teeth.  This  resorp- 
tion  is  accompanied,  as  in  bone,  with  the  production  of  osteoclasts. 

The  portion  of  the  dental  lamina  which  is  not  utilized  in  producing 
enamel  organs  becomes  perforated  and  forms  irregular  outgrowths  (Fig. 
91).  This  disintegration  begins  in  the  front  of  the  mouth  and  spreads 
laterally.  Epithelial  remnants  from  the  lamina  have  been  found  in  the 
gums  at  birth  and  have  been  mistaken  for  glands.  Like  other  epithelial 
remains  they  occasionally  develop  abnormally,  forming  cysts  and  other 
tumors.  The  deepest  part  of  the  lamina,  below  the  enamel  organs  of 
the  permanent  teeth,  is  considered  by  Rose  to  be  a  possible  source  of  a 
third  set,  and  he  states  that  a  case  has  been  reported  to  him  in  which 
such  a  set,  consisting  of  thirty-two  teeth,  developed  on  the  lingual  side 
of  the  permanent  teeth.  The  models  which  Rose  prepared,  showing 
the  enamel  organs  in  various  stages  of  development,  form  the  basis  of 
present  accounts  of  tooth  development.  They  are  described  and  well 
illustrated  in  the  Arch.  f.  mikr.  Anat.,  1891,  vol.  38,  pp.  447-491. 

ENAMEL  ORGAN  AND  ENAMEL. 

The  basal  cells  of  the  oral  epithelium  may  be  followed  as  a  distinct 
layer  over  the  dental  lamina  and  enamel  organ,  as  shown  in  Fig.  92. 
This  suggests  that  the  enamel  organ  should  be  regarded  as  an  infolding 
of  the  oral  epithelium,  and  the  occurrence  of  a  transient  dental  g  oove 
immediately  above  the  lamina  (Fig.  90,  C)  favors  this  interpretation.  The 
basal  surface  of  the  epithelium  of  the  enamel  organ  is  therefore  directed 
toward  the  surrounding  mesenchyma,  and  the  superficial  cells  are  found 
in  the  interior  of  the  organ.  At  first  these  internal  cells  are  in  close 
contact,  like  those  of  ordinary  epithelium,  but  later,  through  an  accumula- 
tion of  gelatinous  intercellular  substance,  they  constitute  a  protoplasmic 
reticulum  which  resembles  mesenchyma,  and  is  known  as  the  enamel 
pulp  (Fig.  93).  No  vessels  or  nerves  penetrate  this  pulp.  On  the  side 
away  from  the  dental  papilla  the  enamel  pulp  is  bounded  by  the  outer 
enamel  cells.  At  first  these  are  typical  cuboidal  epithelial  cells,  but  later 
they  become  flattened  and  transformed  into  a  feltwork  of  pulp  fibers. 
Toward  the  dental  papilla  the  enamel  pulp  is  bounded  by  inner  enamel 
cells,  which  develop  differently  over  the  upper  and  lower  parts  of  the 
tooth  respectively.  Over  the  lower  portion  of  the  dental  papilla  they 
remain  as  cuboidal  or  low  columnar  cells.  Here,  through  a  thinning  of 
the  pulp,  they  are  brought  into  contact  with  the  outer  enamel  cells,  and 


TEETH 


103 


the  two  layers  together  form  the  epithelial  sheath  of  the  root  (Fig.  102). 
Over  the  upper  part  of  the  dental  papilla,  the  inner  enamel  cells  elongate 
and  become  enamel-producing  cells  or  ameloblasts  (Fig.  93). 

The  ameloblasts  produce  enamel  along  their  basal  surfaces,  which 
are  toward  the  dental  papilla,  but  they  become  so  transformed  that 
their  basal  surfaces  appear  like  free  surfaces,  and  the  entire  cells  seem 
inverted.  In  columnar  epithelial  cells  the  nuclei  are  generally  basal, 
and  the  secretion  gathers  near  the  free  surface,  but  in  the  ameloblasts 
these  conditions  are  reversed.  The  nuclei  are  toward  the  enamel  pulp, 


Thickened  —• '-: 

oral 
ithelium. 


Outer  enamel  cells. 

Enamel  pulp 
Inner  enamel  cells 


Free  edge  of  the 
dental  lamina  . 


Papilla. 


PIG.  92.  —  FROM  A  CROSS  SECTION  OF  THE  UPPER  JAW  OF  A  HUMAN  EMBRYO  OF  FIVE  MONTHS.     X  42. 


and  the  latter  forms  a  dense  layer  over  the  ameloblasts,  suggesting  a 
basement  membrane  (Fig.  93).  According  to  Cohn  (Verh.  phys.-med. 
Ges.  Wiirzburg,  1897,  vol.  31,  No.  4)  both  ends  of  the  ameloblasts  are 
encircled  by  terminal  bars.  These  bars  may  be  regarded  as  modifica- 
tions of  the  thin  film  of  cement  substance  found  between  the  ameloblasts. 
Near  the  center  of  each  cell,  and  therefore  on  the  basal  side  of  the  nucleus, 
Cohn  has  described  typical  centrosomes  or  diplosomes. 

Toward  the  dental  papilla  the  protoplasm  of  the  ameloblasts  contains 
granules  or  droplets  which  blacken  with  osmic  acid  and  presumably 
indicate  secretory  activity.  The  basal  surface  of  each  ameloblast  presents 


104 


HISTOLOGY 


a  cuticular  border  and  gives  rise  to  a  tapering  projection  known  as  Tomes' s 
process.  Tomes's  processes  extend  into  the  developing  enamel,  but 
they  may  readily  be  seen  in  specimens  in  which  the  layer  of  ameloblasts 
has  shrunken  away  from  the  enamel,  as  in  Fig.  93.  Around  these  proc- 
esses minute  globules  are  deposited,  which  resemble  the  granules  within 
the  cells,  since  they  blacken  with  osmic  acid.  They  are  described  as, 
composed  of  a  horny  substance  similar  to  that  found  in  the  epidermis. 
This  material  may  become  fibrillar,  and  Tomes's  processes  also  readily 
break  up  into  fibrils.  There  is  therefore  an  uncalcified  fibrillar  layer  of 


Cuticular         Tomes's     Enamel 
border.          processes,    cement.      Calcined, . .  uncalcified  dentine. 


j  Enamel  pulp. 
Outer  enamel  cells. 


Rectangle  enclosing  the  portion 
of  the  tooth  shown  highly  magni- 


Odontoblasts.         Pulp. 
Inner  enamel  cells 

(ameloblasts). 

FIG.  93. — PORTION  OF  A  LONGITUDINAL  SECTION  OF  AN  INCISOR  TOOTH  FROM  A  NEWBORN  KITTEN. 
In  this  section  the  Tomes's  processes  have  shrunken  away  from  the  enamel  cement. 


fied  in  the  adjoining  part  of  the 
figure. 

X  300. 


enamel  next  to  the  ameloblasts.  Further  from  the  ameloblasts  the 
enamel  is  calcified  and  consists  of  rods  known  as  enamel  prisms  (sometimes 
called  enamel  fibers)  which  are  bound  together  by  calcified  matrix  or 
enamel  cement.  The  way  in  which  the  prisms  develop  has  not  been  fully 
determined.  They  have  been  regarded  as  the  calcified  ends  of  the 
ameloblasts  arid  also  as  intercellular  deposits. 

The  formation  of  enamel  begins  at  the  top  of  the  crown  of  each  tooth 
and  spreads  downward  over  its  sides.  If  the  tooth  has  several  cusps,  a 
cap  of  enamel  forms  over  each,  and  these  caps  later  coalesce.  The  enamel 
increases  in  thickness  by  the  elongation  of  the  prisms,  which  extend 
across  it  from  the  inner  to  the  outer  surface. 


TEETH  105 

When  the  tooth  comes  out  through  the  gum,  or  erupts,  the  enamel  is 
covered  with  a  "persistent  capsular  investment"  described  by  Nasmyth 
(1849)  and  called  "Nasmyth's  membrane"  (cuticula  dentis).  Huxley 
studied  this  structure  as  it  covers  the  teeth  in  an  embryo  of  the  seventh 
month  (Trans.  Micr.  Soc.  London,  1853,  v°l-  z>  PP-  I49~I64)-  He  found 
that  the  inner  enamel  cells  could  be  easily  removed,  leaving  the  surface 
of  the  enamel  covered  with  a  finely  wrinkled  or  reticulated  structureless 
membrane.  Upon  adding  strong  acetic  acid  the  membrane  became 
voluminous  and  transparent,  and  was  thrown  into  coarse  folds.  The 
ends  of  the  enamel  prisms  could  be  seen  through  it.  This  dental  cuticula 
is  now  generally  considered  to  be  composed  of  the  last-formed  uncalcified 
ends  of  the  enamel  prisms,  which  are  composed  of  horny  material.  After 
the  eruption  of  the  tooth  it  is  gradually  worn  away,  remaining  longest  in 
the  depressions  of  the  enamel. 

The  fully  developed  enamel  is  the  hardest  substance  in  the  body. 
Several  analyses  have  shown  that  it  contains  less  than  5%  of  organic 
matter.  No  cells  or  protoplasmic  structures  are  found  within  it,  but  it 
exhibits  various  markings,  shown  in  Fig.  94.  The  outer  surface  of  the 
enamel  of  the  permanent  teeth,  especially  on  the  sides  of  the  crown  and 
on  young  teeth,  presents  a  succession  of  circular  ridges  and  depressions, 
which  may  be  seen  with  a  hand  lens.  These  were  discovered  by  Leeuwen- 
hoek  (1687),  whose  figure  of  them  is  reproduced  in  Fig.  94,  A.  He  con- 
sidered that  they  marked  the  intervals  during  the  eruption  of  the  tooth, 
and  wrote,  "For  example,  let  us  assume  that  the  tooth  has  fifty  circles 
or  ridges;  if  this  is  so,  the  tooth  has  been  pushed  through  the  gum  during 
fifty  successive  days  or  months."  This  explanation  is  not  supported  by 
any  evidence. 

The  enamel,  as  seen  in  ground  sections  passing  lengthwise  through 
the  tooth,  shows  numerous  brownish  bands  which  are  broadest  and  most 
distinct  toward  the  free  surface  (Fig.  94,  B).  These  are  the  contour  lines 
or  lines  of  Retzius,  first  described  in  Miiller's  Archiv,  1837  (pp.  486-566). 
The  coarsest  of  them  may  be  seen  with  the  naked  eye,  but  upon  magni- 
fication these  are  resolved  into  a  number  of  finer  lines,  and  many  new 
lines  appear.  Their  direction  is  shown  in  the  figure;  they  arch  over  the 
apex  of  the  crown,  and  on  its  sides  tend  to  be  parallel  with  the  long  axis 
of  the  tooth.  Thus  they  cross  the  enamel  prisms,  and  are  not  the  lines 
along  which  the  enamel  most  readily  fractures.  Apparently  they  indi- 
cate the  shape  of  the  entire  enamel  at  successive  stages  in  its  development, 
and  for  this  reason  they  are  called  contour  lines.  When  Leeuwenhoek's 
ridges  are  present,  the  lines  of  Retzius  end  in  the  furrows  between  them. 
It  was  once  supposed  that  their  brown  color  was  due  to  pigment,  and  it  is 
well  known  that  the  enamel  of  certain  teeth  in  rodents  is  deeply  pigmented 
and  brown.  But  when  the  lines  are  highly  magnified,  no  pigment  granules 


io6 


HISTOLOGY 


are  found.     It  then  appears  that  the  lines  are  due  to  imperfect  calcification 
of  the  enamel  cement,  which  is  often  vacuolated  where  a  line  crosses  it. 

Another  set  of  lines  crosses  the  enamel  radially,  taking  the  shortest 
course  from  the  dentine  to  the  free  surface.  These  radial  lines  are  due 
to  the  arrangement  of  the  enamel  prisms,  and  fractures  of  the  enamel 
tend  to  follow  them.  As  seen  in  reflected  light,  under  low  magnification, 
they  appear  as  alternating  light  and  dark  bands,  often  called  Schreger's 
lines.  The  prisms  in  crossing  the  enamel  are  bent  in  such  a  way  that  they 
are  cut  in  alternating  zones  of  cross  and  longitudinal  sections,  respectively 
(Fig.  94,  C).  These  zones  vary  in  shape  and  sometimes  the  prisms  in 
cross  section  form  an  island  surrounded  by  longitudinal  sections.  Since 
an  entire  prism  cannot  be  isolated  or  included  within  the  limits  of  a  single 
section,  the  course  which  they  take  is  difficult  to  determine.  There  is  no 


FIG.  94. — THE  MARKINGS  OF  THE  ENAMEL  IN  ADULT  TEETH. 


section  of  a  canine 
interglobular  spaces. 


A,  Leeuwenhoek's  figure  showing  ridges  encircling  the  enamel.     B,  Longitudinal  ground 

tooth;  c,  cement;  c.  1.,  contour  lines  (lines  of  Retzius);  d.  c.,  dentinal  canals;  i.  s.,  irucieiuumai  a^cn-ea. 
C,  Longitudinal  section  of  the  enamel  of  an  incisor  tooth,  the  dentinal  surface  being  toward  the  left. 
The  enamel  shows  zones  of  transverse  and  longitudinal  sections  of  enamel  prisms.  D,  Fragment  of 
enamel  showing  prisms  in  longitudinal  view,  slightly  affected  by  hydrochloric  acid.  X  350  (Koelliker). 
E,  Cross  section  of  the  decalcified  enamel  of  a  canine  tooth  from  a  child  of  three  years.  X  350  (Koel- 
liker). F,  Cross  section  of  enamel  prisms  of  a  permanent  molar  from  a  child  of  about  eight  years. 
(Smreker.) 

evidence  that  they  branch,  and  the  greater  surface  which  they  cover  at 
the  periphery  of  the  enamel,  as  compared  with  the  dentinal  surface,  has 
been  explained  by  an  increase  in  the  diameter  of  the  prisms  as  they  pass 
outward.  Such  an  enlargement  is  not  well  marked,  however,  and  is  partly 
offset  by  an  outward  thinning  of  the  interprismatic  cement.  Apparently 
there  is  an  increase  in  the  number  of  ameloblasts  as  the  tooth  becomes 
larger,  and  there  may  be  some  late-formed  enamel  prisms  which  do  not 
reach  the  dentinal  surface.  The  plan  according  to  which  the  prisms  bend 
is  discussed  in  Koelliker's  Gewebelehre  (6th  ed.)  but  it  has  never  been 
fully  explained. 

The  individual  enamel  prisms,  when  seen  lengthwise,  exhibit  trans- 
verse markings.  These  may  be  made  out  in  ground  sections,  but  they 
become  more  evident  after, the  prisms  have  been  treated  with  acid  (Figs. 
94,  D  and  99).  They  have  been  regarded  as  artificial  products,  but  prob- 
ably they  indicate  successive  stages  in  the  elongation  of  the  prism.  Fre- 


TEETH 


107 


quently  the  prisms,  when  isolated,  appear  beaded,  with  transverse  bands 
at  the  places  of  constriction. 

When  seen  in  cross  section  the  prisms  have  highly  refractive  outlines, 
from  3-6  /A  in  diameter.  They  were  formerly  described  as  polygonal 
and  primarily  hexagonal  (Fig.  94,  E)  but  Smreker  finds  that  they  are 
crescentic,  as  shown  in  Fig.  94,  F  (Arch.  f.  mikr.  Anat.,  1905,  vol.  66, 
pp.  312-331).  The  convex  side  of  the  crescent,  along  which  the  interpris- 
matic  cement  'is  most  abundant,  is  always  toward  the  dentine.  The 
hollow  of  the  crescent  receives  an  adjacent  prism  which  appears  to  have 
been  pressed  into  it.  Isolated  prisms  of  this  sort  are  therefore  hollowed 
out  on  one  side,  and  it  is  possible  that  they  connect  with  one  another  by 
flanges  or  bridges  (von  Ebner,  Arch.  f.  mikr.  Anat.,  1905.  vol.  67,  pp.  18-81). 

DENTAL  PAPILLA,  DENTINE,  AND  PULP. 

The  dental  papilla  has  already  been  described  as  a  mass  of  dense 
mesenchyma,  enclosed  and  probably  moulded  by  the  enamel  organ.  At 
the  end  of  the  fourth  month,  shortly  before  the  formation  of  enamel  has 
begun,  the  outermost  cells  of  the  papilla  become 
elongated  and  arranged  in  an  epithelioid  layer. 
Since  they  produce  the  dentine,  which  is  the 
principal  part  of  the  tooth,  these  cells  are  known 
as  odontoblasts .  At  first  they  rest  against  the 
inner  enamel  cells.  Later  a  thin  layer  of  pre- 
dentine  extends  like  a  membrane  between  the 
ameloblasts  and  odontoblasts;  it  is  seen  as  a 
white  line  in  Fig.  92.  As  the  layer  of  predentine 
widens  and  becomes  calcified,  the  odontoblasts 
remain  on  its  inner  surface,  which  is  toward  the 
pulp.  Five  of  them  are  shown  in  Fig.  95, 
together  with  their  branching  processes,  one  of 
which  proceeds  from  the  cuticular  border  of  each 
cell  and  occupies  a  canal  in  the  dentine.  These 
dental  or  dentinal  canals  (canaliculi  denlales)  are 
readily  observed  in  adult  teeth.  Their  existence,  and  the  fact  that  they 
open  into  the  pulp  cavity,  were  recorded  by  Leeuwenhoek  in  1687. 
"The  presence  of  fibrils  of  soft  tissue  within  the  dentinal  tubes"  was 
established  by  Tomes  in  1856  (Phil.  Trans.,  pp.  515-522).  He  found 
that  if  a  section  of  a  fresh  tooth  is  placed  in  dilute  hydrochloric  acid  and 
then  torn  across  the  tubes,  fibrils  will.be  seen  projecting  from  the  broken 
edges;  and  that  if  the  pulp  is  pulled  away  from  the  dentine,  fibrils  can  be 
drawn  out  from  the  tubes.  By  the  latter  method  the  cells  shown  in  Fig. 
96  were  obtained.  The  fibers  within  the  dentinal  canaliculi  are  called 
dentinal,  dental  or  Tomes' s  fibers. 


FIG.  95. — FIVE  ODONTOBLASTS, 
FROM  WHICH  TOMES'S  FIBERS 
EXTEND  UPWARD  INTO  THE 
DENTINE,  FROM  A  TOOTH  OF  A 
NEWBORN  CAT.  (Prenant.) 


io8 


HISTOLOGY 


Recently  von  Korff,  with  special  methods,  has  demonstrated  another 
sort  of  fibers  which  lie  between  the  odontoblasts  and  pass  from  the  pulp 
into  the  predentine  (Fig.  97,  A).  The  fibers  are  apparently  collagenous 


FIG.  96. 

Six  odontoblasts  with  dentinal  (or  Tomes's) 
fibers,  "f.  p.,  pulp  processes.  From  the  pulp 
at  birth.  X  240. 


FIG.  97- — THE  DEVELOPMENT  OF  DENTINE 
IN  PIG  EMBRYOS.  (After  v.  Korff.) 

d.,  Calcified  dentine;  e.  c.,  inner  enamel 
cells |  f.,  fibrous  ground  substance  of 
dentine;  od.,  odontoblasts;  p.,  mesen- 
chymal  cells. 


and  among  them,  immediately  beneath  the  layer  of  enamel  cells,  cal- 
careous granules  begin  to  be  deposited  (Fig.  97,  B).  These  granules  be- 
come abundant,  and  fill  the  ground  substance  of  the  dentine.  Von  Korff 
concludes  that  it  is  not  the  odontoblasts  but  the  fibrils 
of  the  pulp  which  give  rise  to  the  dentine,  and  similarly 
he  finds  that  in  bone  the  osteogenic  fibers  develop  from 
the  surrounding  mesenchyma  rather  than  from  osteo- 
blasts  (Arch.  f.  mikr.  Anat,  1907,  vol.  69,  pp.  515-543). 
Studnicka  agrees  with  von  Korff  that  " the  odontoblasts 
are  really  gland  cells,  which  are  only  secondarily  con- 
cerned in  the  formation  of  dentine  and  do  not  produce 
ground  substance;  their  processes  (the  Tomes's  fibers) 
serve  to  convey  certain  nutrient  material  to  the  parts 
far  removed  from  the  inner  surface,  and  thus  nourish 
the  dentine."  (Anat.  Anz.,  1909,  vol.  34,  pp.  481-502.) 
Von  Ebner,  however,  maintains  that  von  Korff's  fibers 
are  produced  by  the  odontoblasts  as  part  of  the  process 
of  dentine  formation. 

Other  very  fine  collagenous  fibrils  in  the  dentinal 
matrix  are  arranged  like  the  decussating  fibers  in  the 
lamellae  of  bone.  They  cross  one  another  as  they  run 
longitudinally  in  the  successively  deposited  layers  of 
dentine.  These  layers  are  sometimes  marked  out  by  distinct  contour 
lines,  the  direction  of  which  is  shown  in  Fig.  98.  They  indicate  the  shape 
of  the  entire  dentine  at  various  stages  in  its  development,  and  show  that 


FIG.  98. — DIAGRAM  OF 
THE  ARRANGEMENT 
OF  THE  DENTINAL 
LAMELL/E  AND 
CONTOUR  LINES  IN 
AN  INCISOR.  (Koel- 
liker.) 


TEETH 


the  root  of  the  tooth  forms  after  the  crown  is  essentially  complete.  The 
innermost  layers  are  formed  last.  In  addition  to  the  contour  lines,  den- 
tine seen  in  reflected  light  shows  the  radial  Schreger's  lines,  which  follow 
the  course  of  the  dentinal  canals  but  are  said  to  be  due  to  the  fibrillar 
structure  of  the  matrix  between  them. 

Dentine  when  fully  developed  is  not  so  hard  as  enamel  and  contains 
a  much  larger  amount  of  organic  matter  (approximately  25%).  When 
the  inorganic  substances  are  removed  from  enamel,  the  remaining  tissue 
scarcely  holds  together,  but  dentine  and  bone,  when  so  treated,  leave  a 
gelatinous  matrix  which  preserves  the  form  of  the  original  object.  The 
dentinal  canaliculi  pass  radially  through  the  dentine,  often  following  a 
somewhat  S-shaped  course  as  shown  in  Fig.  94,  B.  In  addition  to  these 
primary  curves,  they  may  show  spiral  twists  and  secondary  curves.  As 
they  cross  the  dentine,  they  divide  dichotomously  a  few  times  and  give 
off  many  slender  lateral  branches,  some  of  which  anastomose  with  those 
from  adjacent  canaliculi  (Fig.  99).  They  finally  become  very  slender 


33  2  I 


Enamel  prisms. 


Dentine.  Enamel. 

FIG.  99. — FROM  A  LONGITUDINAL  SECTION  OF  THE  LATERAL 
PART  OF  THE  CROWN  OF  A  HUMAN  MOLAR  TOOTH. 
X  240. 

I,  Dentinal  canaliculi,  some  extending  into  the  enamel;  2, 
globules  of  calcified  dentine  projecting  into  the  inter- 
globular  spaces,  3. 


Cement. 


FIG.  100. — FROM  A  LONGITUDINAI   SEC- 
TION   OF     THE     ROOT    OF    A    HUMAN 

MOLAR  TOOTH.     X  240. 
i,  Dentinal  canaliculi   interrupted  by  a 
stratum   with   many  small  interglobular 
spaces,  2.     3,  bone  lacunae  and  canaliculi. 


and  generally  end  blindly,  but  some  terminal  loops  have  been  described. 
Each  canal  is  surrounded  by  a  resistant  uncalcified  layer  known  as  Neu- 
mann's sheath.  This  sheath  may  be  isolated  with  acids,  and  thus  it  is 
comparable  with  the  " corpuscles"  of  bone  and  the  capsules  of  cartilage. 
It  is  difficult  to  determine  whether  the  processes  from  the  odontoblasts 
extend  the  whole  length  of  the  canaliculi,  but  they  are  believed  to  do  so. 
Tomes  observed  that  the  peripheral  portion  of  the  dentine  is  more  sen- 
sitive than  the  deeper  part,  and  considered  that  the  fine  ramifications  of 
the  odontoblasts  respond  like  nerve  fibers  to  stimulation.  Nerves 
have  been  traced  to  the  odontoblast  layer  at  the  base  of  the  dentine,  but 
it  is  doubtful  whether  they  extend  into  the  dentinal  canals  as  some  have 
reported. 


110  HISTOLOGY 

The  contact  between  the  dentine  and  enamel  is  usually  quite  smooth. 
Each  enamel  prism  rests  in  a  shallow  socket  on  the  dentinal  surface, 
and  in  places  the  dentinal  canals  extend  into  basal  clefts  in  the  enamel 
cement.  A  short  distance  beneath  the  enamel  the  dentine  exhibits  a 
layer  of  spaces,  which  in  ground  sections  are  filled  with  air  and  appear 
black  (Fig.  94,  B,  i.s.).  They  occur  along  the  contour  lines,  and 
are  due  to  imperfect  calcification  of  the  cement  in  that  region  of  the 
matrix  which  was  the  first  to  form.  Each  space  is  bounded  by  spherules  of 
calcified  matrix  which  project  into  it  from  all  sides,  and  the  cavities  are 
therefore  known  as  inter  globular  spaces  (Fig.  99).  Toward  the  root  of  the 
tooth  they  are  smaller  and  more  numerous  than  in  the  crown.  They  are 
said  to  be  particularly  abundant  in  poorly  developed  teeth. 

The  pulp  consists  of  a  fine  network  of  reticular  tissue  together  with  the 
peripheral  layer  of  odontoblasts  already  described.  The  odontoblasts 
persist  throughout  life,  and  may  continue  to  produce  dentine  so  that  the 
root  canals  may  become  nearly  or  quite  obliterated.  They  are  also  active 
in  repairing  injuries.  Some  of  the  late-formed  dentine  contains  blood 
vessels  and  resembles  bone,  so  that  it  has  been  called  osteo-dentine.  The 
odontoblasts  connect  with  one  another  and  with  the  rest  of  the  pulp  by 
protoplasmic  processes.  The  pulp  tissue  is  free  from  elastic  fibers  and 
from  bundles  of  white  fibers.  It  is  very  vascular.  The  small  arteries 
entering  the  apical  foramina  send  capillaries  close  to  the  odontoblasts,  but 
normally  they  do  not  enter  the  dentine.  Lymphatic  vessels,  according  to 
Schweitzer,  are  found  by  injection  to  begin  as  a  tuft  of  branches  in  the 
pulp  of  the  crown;  they  empty  into  one  or  a  few  very  wide  vessels  passing 
through  the  root  (Arch.  f.  mikr.  Anat,  1907,  vol.  69,  pp.  807-908).  The 
nerves  of  the  pulp  are  the  medullated  dental  branches  of  the  alveolar  nerves, 
which  enter  through  the  apical  foramina,  lose  their  sheaths  and  form  a  loose 
plexus  beneath  the  odontoblasts,  between  which  they  terminate  in  free 
endings. 

DENTAL  SAC,  CEMENT,  AND  PERIOD ONTAL  TISSUE. 

Each  embryonic  tooth,  consisting  of  its  enamel  organ  and  papilla,  is 
completely  surrounded  by  mesenchyma,  which  extends  from  the  oral 
epithelium  to  the  bony  trabeculae  of  the  developing  jaw  (Fig.  101).  This 
mesenchyma  gives  rise  to  the  dental  sacs  enclosing  the  teeth;  each  sac 
consists  of  a  dense  outer  layer  and  a  loose  inner  layer  of  young  connective 
tissue  (Fig.  102).  Toward  the  base  of  the  dental  papilla  the  tissue  of  the 
sac  is  separated  from  the  dentine  by  the  epithelial  sheath,  which  is  a  part 
of  the  enamel  organ.  After  the  crown  of  the  tooth  is  well  developed,  the 
epithelial  sheath  disintegrates  or  becomes  penetrated  by  cells  of  the  dental 
sac,  which  are  then  transformed  into  osteoblasts  and  deposit  bone  directly 


TEETH  III 

upon  the  outer  surface  of  the  dentine.  This  bone  is  a  part  of  the  tooth  and 
is  known  as  the  substantia  ossea  or  cement.  It  is  thinnest  at  the  neck  of 
the  tooth,  and  increases  in  thickness  downward  toward  the  apex  of  the  root, 
over  which  it  forms  a  considerable  cap  (Fig.  88).  The  deeper  part  of  the 
root  develops  after  the  eruption  of  the  crown. 

The  cement  contains  typical  bone  cells,  enclosed  in  large  lacunae  which 
connect  with  one  another  through  canaliculi  (Fig.  100).  The  dentinal 
surface  sometimes  appears  resorbed  and  the  dental  canaliculi  then  end 
abruptly;  occasionally  they  appear  to  anastomose  with  those  of  the  cement. 


Cross  section  of  the 
orbicularis  oris  muscle. 


I Labial  gland. 


Dental  lamina. 


Enamel  organ. 


Enamel. 


FIG.  101. — VERTICAL  SECTION  THROUGH  THE  LIP  AND  JAW  OF  A  HUMAN  EM- 
BRYO OF  Six  AND  A  HALF  MONTHS.     X  9. 

The  lamellae  of  the  cement,  which  are  seldom  well  marked,  are  concentric- 
ally placed  around  the  root.  In  young  teeth  Haversian  canals  are  absent, 
but  in  old  teeth  they  occur  in  the  outer  layers  near  the  apex  of  the  root. 
Connective  tissue  fibers,  comparable  with  Sharpey's  fibers  in  bone,  pass 
radially  through  the  cement.  They  cross  the  dental  sac  and  enter  the 
bone  of  the  alveolus,  thus  binding  the  tooth  to  its  socket 

As  the  tooth  enlarges  and  fills  the  socket,  the  dental  sac  becomes  re- 
duced to  a  thin  layer  consisting  of  the  alveolar  periosteum  externally  and 
the  dental  periosteum  internally,  with  vascular  connective  tissue  between. 
Frequently  these  are  described  as  a  single  layer.  It  may  contain  fragments 
of  the  epithelial  sheath.  It  has  few  elastic  fibers,  but  is  well  supplied  with 


112 


HISTOLOGY 


vessels  and  nerves  which  are  branches  of  those  about  to  enter  the  apical 
foramen.  Around  the  neck  of  the  tooth,  dense  connective  tissue  forms  the 
circular  ligament  (Lig.  circular e  dentis). 

The  gum  (gingiva)  is  the  part  of  the  lining  of  the  mouth  which  sur- 
rounds the  tooth.     It  is  covered  by  the  stratified  oral  epithelium,  in  which 


Dental  sac. 


Outer  layer.       Inner  layer. 


Outer  enamel  cells. 

Enamel  pulp. 
Inner  enamel  cells. 


m 

Ml Enamel. 


Epithelial 
sheath. 


Dentine 


Odontoblasts 


Dental  papilla 
(future  pulp) . 


Blood  vessel. 
Bony  trabecula  of  the  lower  jaw 


FIG.  102. — LONGITUDINAL  SECTION  OF  A  DECIDUOUS  TOOTH  OF  A  NEWBORN  DOG.     X  42. 
The  white  spaces  between  the  inner  enamel  cells  and  the  enamel  are  artificial,  and  due  to  shrinkage. 

intercellular  bridges  are  well  developed,  and  this  epithelium  rests  on  tall 
connective  tissue  elevations  or  papillae.  There  are  no  glands  in  the  gums. 
When  the  tooth  erupts  it  makes  a  hole  through  the  epithelium,  but  the 
margins  of  the  aperture  become  inverted.  Thus  the  epithelium  extends 


TEETH 

close  to  the  tooth  and  turns  down  as  a  sheath  surrounding  the  neck.  At 
the  level  of  the  upper  part  of  the  cement  it  ends  abruptly.  The  connective 
tissue  of  the  gums  blends  below  with  the  circular  ligaments.  It  contains 
few  elastic  fibers,  but  is  very  vascular  and  is  often  infiltrated  with  lympho- 
cytes. Its  lymphatic  vessels  drain  outward,  along  the  margin  of  the  cheek 
and  gums,  and  inward,  over  the  floor  or  roof  of  the  mouth,  as  shown  by 
Schweitzer. 

MUSCULAR  TISSUE. 

Contractility  is  a  fundamental  property  of  protoplasm.  In  muscle  cells 
it  attains  its  highest  development.  Muscle  cells  are  elongated  structures, 
known  as  muscle  fibers,  which  contain  numerous  longitudinal  fibrils  within 
their  protoplasm.  By  the  shortening  of  these  fibrillated  cells,  muscular 
action  results.  The  muscle  fibrils,  or  myoflbrils,  may  be  free  from  trans- 
verse markings,  as  in  smooth  muscle;  or  they  may  exhibit  a  succession  of 
dark  and  light  transverse  bands,  as  in  striated  muscle.  Smooth  muscle 
fibers  enter  into  the  formation  of  the  viscera,  and  their  action,  almost 
without  exception,  is  involuntary.  Striated  muscle,  in  so  far  as  it  consti- 
tutes the  entire  system  of  skeletal  muscles,  is  voluntary,  or  under  the  control 
of  the  will,  but  the  striated  fibers  of  the  diaphragm  and  upper  part  of  the 
oesophagus  are  apparently  involuntary.  The  special  form  of  striated  mus- 
cle, known  as  cardiac  muscle,  which  makes  the  bulk  of  the  heart  and  extends 
some  distance  in  the  wall  of  the  pulmonary  veins,  is  involuntary.  The 
three  principal  forms  of  muscle,  smooth,  skeletal,  and  cardiac,  are  meso- 
dermal  in  origin.  Within  the  basement  membrane  of  the  sweat  glands 
there  are  elongated  ectodermal  cells  which  have  been  described  as  smooth 
muscle  fibers,  but  their  contractile  nature  is  still  questioned.  It  is  well 
established,  however,  that  the  muscles  of  the  iris,  which  control  the  size  of 
the  pupil,  are  derived  from  ectodermal  cells  which  bud  off  from  those  form- 
ing the  optic  cup  Ectodermal  muscles  in  man  are  limited  to  these 
examples. 

SMOOTH  MUSCLE. 

Smooth  muscle  fibers  are  derived  from  mesenchymal  or  young  connec- 
tive tissue  cells.  Usually  they  are  produced  in  layers  which  surround 
some  tubular  organ,  such  as  a  blood  vessel,  duct,  or  a  part  of  the  digestive 
tube.  The  fibers  in  these  layers  are  generally  parallel,  and  are  usually 
either  circular  or  longitudinal  in  relation  to  the  organ  which  they  envelop. 
Occasionally  they  are  oblique,  or  irregularly  interwoven.  Fibers  which 
encircle  an  organ  are  called  circular  or  transverse  fibers;  they  may  be  cut 
across  or  split  lengthwise  according  to  the  plane  in  which  the  organ  is 
sectioned.  The  same  is  true  of  the  longitudinal  fibers,  which  run  length- 
wise of  the  organ. 

8 


114  HISTOLOGY 

The  formation  of  smooth  muscle  may  be  studied  advantageously  in 
the  oesophagus  of  pig  embryos,  and  its  development  in  this  position 
has  been  carefully  described  by  Miss  McGill  (Internat.  Monatschr.  f. 
Anat.  u.  PhysioL,  1907,  vol.  24,  pp.  209-245).  A  part  of  a  longitudinal 
section  of  the  oesophagus  of  a  27-mm.  pig  is  shown  in  Fig.  103.  In  such 
a  section  the  developing  longitudinal  smooth  muscle  fibers  or  myoblasts 
are  cut  lengthwise  (s.l.) ;  and  the  circular  fibers,  which  form  a  layer  internal 
to  the  longitudinal  fibers,  are  cut  across  (s.c.).  The  loose  mesenchymal 
network,  from  which  these  fibers  arise,  is  continuous  with  them  above 
and  below.  A  third  thin  layer  of  muscle  fibers  is  forming  at  m.m.,  and 
at  the  top  of  the  figure,  the  entodermal  epithelium  which  lines  the 
oesophagus  has  been  included,  together  with  the  basement  membrane 
beneath  it. 

In  becoming  smooth  muscle  cells,  the  mesenchymal  cells  change  from 
a  stellate  to  a  spindle-shaped  form  and  come  closer  together,  but  they  do 
not  lose  their  protoplasmic  connections  with  one  another.  In  the  outer 
part  of  their  protoplasm  coarse  border  fibrils  or  myoglia  fibrils  are  produced, 
which  are  similar  to  the  fibroglia  fibrils  of-  connective  tissue  (p.  64). 
According  to  Meves,  the  fibroglia  and  myoglia  are  jdentical.  The  latter 
are  at  the  periphery  of  the  muscle  cells  and  pass  from  one  cell  to  another 
for  long  distances.  These  fibrils  may  be  strikingly  demonstrated  in  the 
oesophagus  of  a  24-mm.  pig,  stained  with  phospho-tungstic  acid  haema- 
toxylin. 

The  coarse  fibers  shown  by  Miss  McGill  in  both  the  circular  and  longi- 
tudinal muscle  layers  in  Fig.  103  are  "often  found  lying  in  part  near  the 
surface  of  the  cell,  resembling  the  border-fibrils  of  Heidenhain."  She 
states  that  they  are  produced  by  a  coalescence  of  granules  within  the 
protoplasm,  forming  at  first  spindle-shaped  bodies  which  later  join  end 
to  end,  making  varicose  fibers.  Subsequently  they  become  smooth. 
They  may  split  into  fine  fibrils,  and  usually  they  decrease  in  number  as 
the  embryo  grows  older.  "In  places  they  may  be  entirely  absent  in  the 
adult  tissue;  rarely  they  are  abundant." 

In  addition  to  the  peripheral  myoglia  fibrils,  the  protoplasm  of  smooth 
muscle  cells  contains  fine  longitudinal  fibrils,  which  have  been  de-- 
scribed  as  the  active  agents  in  muscular  contraction.  Thus  Miss  McGill 
finds  that  in  the  contracted  portions  of  the  muscle  fibers  the  myofibrillae 
show  "a  distinct  increase  in  caliber."  She  states  that  the  fine  myofibrils 
do  not  arise  until  the  pig  embryo  reaches  a  length  of  about  30  mm.  They 
are  apparently  homogeneous  from  the  beginning,  and  are  distributed  uni- 
formly throughout  the  protoplasm.  Some  of  them  are  shown  in  the  muscle 
layer  m.m.  in  Fig.  103.  Ordinarily  these  fibrils  are  indistinguishable  in  the 
close-grained,  deeply  staining  protoplasm  which  characterizes  the  muscle 
cells. 


SMOOTH  MUSCLE 


Along  the  sides  of  the  muscle  fibers  there  are  at  first  protoplasmic 
processes  which  bind  them  together.  Later  these  seem  to  be  replaced 
by  white  fibers,  like  those  of  ordinary  connective  tissue.  They  form  a 
network  investing  the  muscle  cells,  as  shown  in  Fig.  104.  This  inter- 
muscular  reticulum,  produced  directly  from  the  muscle  fibers,  is  unusually 
well  shown  in  the  walls  of  the  blood  vessels  in  the  umbilical  cord.  To 
some  extent,  according  to  Miss  McGill,  it  is  produced  from  special  mesen- 


me  s. 


FIG.    103. — FROM  A  LONGITUDINAL  SECTION  OF 
THE  (ESOPHAGUS  OF  A  27-MM.  PIG  EMBRYO. 

X  700.  (After  McGill.) 
b.    m.,    Basement    membrane;    epi.,   epithelium; 

mes.,  mesenchyma;  m.  m.,  muscularis  mucosae; 

n.,  nerve  cells;  s.  c.,  circular  smooth  muscle 

cut  across;  s.  1.,  longitudinal  smooth  muscle 

cut  lengthwise. 


FIG.  104. — FIBROUS  TISSUE  IN 
RELATION  WITH  SMOOTH 
MUSCLE  FIBERS,  FROM  THE 
BLADDER  OF  A  PIKE.  (After 
Prenant.) 

c.f  Connective  tissue  network; 
n.,  p.,  f.,  nucleus,  granular 
protoplasm,  and  fibrillar  pro- 
toplasm of  a  muscle  cell. 


chymal  cells  within  the  muscle  layer,  which  develop  into  connective  tissue 
cells.  In  many  layers  of  smooth  muscle,  however,  connective  tissue  cells 
are  difficult  to  demonstrate.  Finally  it  should  be  noted  that  elastic 
fibers  are  found  between  the  muscle  cells.  They  vary  greatly  in  number, 
being  especially  abundant  in  the  walls  of  arteries. 

From  what  has  been  said,  it  is  evident  that  smooth  muscle  retains  its 
original  syncytial  nature,  and  that  to  some  extent  it  resembles  connective 
tissue.  It  consists  of  elongated  contractile  cells  which  are  joined  together, 
especially  toward  their  extremities,  by  'myoglia  fibrils,  and  which  are 
bound  together  laterally  by  a  white  fibrous  network  containing  inter- 


Il6  HISTOLOGY 

spersed  elastic  fibers.  These  features,  which  are  essential  for  understand- 
ing the  action  of  smooth  muscle,  are  usually  difficult  to  observe  in  the  com- 
pact tissue  of  the  adult. 

Smooth  muscle  fibers  in  the  adult  are  fusiform,  cylindrical  or  slightly 
flattened  cells,  varying  in  length  from  about  0.02  mm.  in  some  blood 
vessels  to  approximately  0.5  mm.  in  the  pregnant  uterus.  In  the  intestine 
they  are  said  to  measure  about  0.2  mm.  Their  diameter,  through  the 
widest  part,  is  from  4-7  /x.  Owing  to  the  length  of  these  fibers  and  the 
fact  that  they  are  not  perfectly  straight,  they  are  seldom  wholly  included 
in  a  single  section.  Moreover  they  are  usually  so  closely  packed  that  their 
outlines  are  hard  to  follow.  They  may  be  isolated,  however,  by  treating 
fresh  tissue  with  a  35%  aqueous  solution  of  potassium  hydrate,  or  20% 
nitric  acid.  The  fibers  when  shaken  apart  appear  as  in  Fig.  105.  Owing 


FIG.  105. — SMOOTH  MUSCLE  FIBERS  FROM  THE  SMALL  INTESTINE  OF 
A  FROG.     X   240. 

to  the  readiness  with  which  they  may  be  disassociated,  the  existence  of 
connections  between  them  has  sometimes  been  overlooked  or  under- 
estimated; but  it  is  evident  that  independent  cells,  by  shortening  cannot 
cause  the  contraction  of  a  tube.  Branching  fibers  have  been  isolated 
from  the  aorta,  and  are  said  to  occur  also  in  the  ductus  deferens  and 
bladder. 

The  fibers  when  sectioned  longitudinally  (see  Fig.  177,  p.  186)  some- 
what resemble  connective  tissue,  from  which  they  may  be  distinguished 
by  the  staining  and  texture  of  their  protoplasm  and  the  position  of  their 
nuclei,  which  are  within  the  fibers.  With  haematoxylin  and  eosin  the  mus- 
cle substance  takes  a  deeper  and  more  purple  stain  than  the  connective 
tissue  fibers,  and  it  is  not  so  refractive.  In  doubtful  cases  Mallory's  con- 
nective tissue  stain  may  be  used,  which  colors  the  muscle  substance  red  and 
the  white  fibrous  tissue  blue. 

The  nuclei  of  smooth  muscle  fibers  are  elliptical  or  rod-like  bodies,  con- 
taining a  characteristic  chromatic  reticulum  and  sometimes  several  nu- 
cleoli  (Fig.  9,  A,  p.  10).  When  the  muscle  fiber  contracts,  the  nucleus 
shortens  and  broadens,  but  according  to  measurements  made  by  Miss 
McGill  (Anat.  Rec.,  1909,  vol.  3,  pp.  633-635)  there  is  no  change  in  its 
volume.  She  finds,  however,  that  the  chromatin  tends  to  collect  at  the 
poles  of  the  contracted  nucleus,  and  states  that  "the  nucleus  appears  to 
take  an  active  part  in  the  process  of  contraction. "  Frequently  spirally 
twisted  or  bent  nuclei  are  found  in  layers  of  contracted  muscle  (Fig.  106) 
and  they  have  been  regarded  as  occupying  contracted  fibers.  is 


SMOOTH   MUSCLE  117 

probable,  however,  that  the  spiral  nuclei  occur  in  relaxed  fibers,  which 
have  been  crumpled  together  by  the  contraction  of  adjacent  fibers." 
Along  one  side  of  the  nucleus  the  centrosome  may  be  found,  occupying 
a  shallow  indentation  of  the  nuclear  membrane. 

At  the  poles  of  the  nuclei  there  is  often  an  accumulation  of  granular 
protoplasm  (Fig.  104,  p.  115)  which  is  sometimes  pigmented.  The  fibrils 
diverge  to  pass  by  the  nucleus,  and  the  granular  protoplasm  occupies  the 
conical  non-fibrillated  space  which  is  thus  produced. 

The  surface  of  the  smooth  muscle  fibers  is  covered  by  -^^ZZMMl-ZZ* 
a  delicate  membrane,  which  is  sometimes  thrown  into 
transverse    wrinkles    by   the    contraction    of    the   fiber. 
Possiblv  the  fibrils  terminate  in  it.     They  do  not  appear  _ 

J  FIG.   1  06.  —  NUCLEI 


to  become  more  compact  as  they  extend  into  the  tapering       SBSFIBERS 
ends  of  the  fibers  and  presumably  they  do  not  all  extend       ™A*TBRYOFA 
the  whole  length  of  the  cell. 

In  transverse  sections  the  fibers  present  rounded  or  polygonal  outlines 
(Fig.  107).  They  vary  in  size,  since  some  are  sectioned  through  the 
tapering  extremity  and  others  through  the  thick  central  part  which 
contains  the  nucleus.  In  the  figure  the  substance  between  the  fibers  ap- 
pears solid,  and  it  has  sometimes  been  described  as  cement,  or  as  a  mem- 
brane rather  than  as  a  reticulurh. 

The  relation  of  the  myoglia,  reticulum  and  muscle  fibers  to  the  process 
of  contraction  has  never  been  adequately  explained.  In  the  intestine,  with 
the  normal  accumulation  of  food,  the  diameter  of  the  tube  becomes  four 
^  _  times  as  great  as  in  the  contracted  state, 

and  the  muscle  layer  becomes  reduced 
to  somewhat  less  than  one-fourth  of  its 
original    thickness.      The  muscle  cells 
appear  to  slip  by  one  another  and  to 
B    form  a  layer  only  a  few  fibers  thick. 
After  a  certain  amount  of  distention 
PIG.  107.—  CROSS  SECTION  OF  SMOOTH  MUSCLE    the  tube  will  expand  no  further,  and 

FIBERS  FROM  THE  STOMACH.     X  560.  111  *L 

a,  Connective  tissue  septum;  b,  section  of  a      added     PrCSSUre     CaUSCS     it    tO    rupture. 

IbS  t?rlaih%tenuucieuuss:  "'  section  of  a    Presumably  the  elastic  and  white  fibers 

aid   in   restoring   the    normal    caliber. 

With  extreme  contraction,  however,  the  white  and  elastic  fibers  no  longer 
aid  the  muscles,  but  become  crumpled  into  coarse  folds,  as  seen  fre- 
quently in  contracted  arteries.  As  to  the  muscle  fibers  themselves, 
Meigs  concludes  that  during  contraction  fluid  passes  from  them  into  the 
intercellular  spaces,  so  that  the  fibers  shrink  in  size  and  become  darker;  he 
states  that  they  decrease  greatly  in  length  but  remain  of  about  the 
same  diameter,  while  the  spaces  between  the  fibers  become  larger 
(Amer.  Journ.  Physiol.,  1908,  vol.  22,  pp.  477-499).  According  to  Miss 


Il8  HISTOLOGY 

McGill,  the  deeply  staining  nodular  thickenings  of  muscle  fibers  indicate 
a  normal  form  of  contraction  in  which  the  fiber  does  not  contract  as  a 
whole,  but  a  wave  of  contraction  passes  over  it.  In  these  contraction 
nodes  the  diameter  of  the  fiber  becomes  increased  (Amer.  Journ.  Anat., 
1909,  vol.  9,  pp.  493-545).  The  enlargement  of  such  muscular  tubes  as 
the  vessels  and  intestine  appears  to  be  passive  and  due  respectively  to 
the  pressure  of  the  blood  or  food  within.  After  extreme  contraction  the 
elastic  tissue  probably  serves  to  dilate  the  tube  to  a  certain  size. 

Smooth  muscle  is  nourished  by  capillary  blood  vessels  which  tend  to 
follow  the  course  of  the  fibers,  and  it  is  innervated  by  slender  branches  of 
the  sympathetic  nervous  system. 

SKELETAL  MUSCLE. 

The  skeletal  muscles  develop  primarily  from  the  mesodermic  somites, 
which  have  been  briefly  described  in  a  previous  section  (p.  39).  The  trans- 
formation of  a  portion  of  each  of  these  blocks  of  tissue  into  layers  and  masses 
of  skeletal  muscle  fibers  has  recently  been  reviewed  by  Williams,  from  whose 
work  Fig.  108  has  been  taken  (Amer.  Journ.  Anat.,  1910,  vol.  n,  pp.  55- 
100).  In  Fig.  108,  A,  the  core  of  the  somite  has  fused  with  the  ventral 
and  medial  walls  of  the  mass,  and  the  tissue  thus  formed  is  streaming 
over  the  aorta  and  toward  the  notochord.  This  tissue,  the  sclerotome, 
becomes  mesenchyma  and  gives  rise  to  smooth  muscle  and  various  other 
mesenchymal  derivatives.  In  the  part  of  the  somite  left  in  place,  near 
the  groove  x,  the  striated  muscle  fibers  begin  to  develop.  The  cells  here 
elongate  at  right  angles  with  the  plane  of  the  figure,  and  thus  lengthwise 
of  the  embryo.  In  an  older  stage  (Fig.  108,  B)  these  myoblasts  have 
multiplied  and  have  begun  to  form  a  plate  of  muscle  tissue,  the  myotome, 
which  extends  ventrally  as  shown  in  C  and  D.  The  dorso-lateral  wall 
of  the  somite  has  meanwhile  become  a  plate  of  tissue,  the  dermatome,  which 
with  the  myotome  associated  with  it,  is  often  called  the  dermo-myotome. 
The  dermatome  according  to  Bardeen  produces  only  striated  muscle 
fibers;  Williams  finds  that  it  forms  only  dermal  connective  tissue,  and 
others  consider  that  it  gives  rise  both  to  muscle  and  connective  tissue. 
The  myotome  is  "entirely  transformed  into  muscle  fibers."  The  way 
in  which  the  myotomes  extend  ventrally  and  break  up  into  the  ventro- 
lateral  trunk  and  neck  musculature,  and  the  longitudinal  fusion  and 
splitting  of  the  dorsal  part  of  the  myotomes  to  produce  the  deep  back 
muscles  of  the  trunk  and  neck,  have  been  described  by  Warren  Lewis 
(Keibel  and  Mall,  Human  Embryology,  1910).  The  skeletal  muscles 
of  the  limbs  have  usually  been  described  as  arising  from  cells  which  have 
migrated  into  the  limbs  from  the  ventral  part  of  the  myotomes.  If  this 
takes  place  the  cells  which  migrate  become  indistinguishable  from  mesen- 


SKELETAL  MUSCLE 


chymal  cells,  but  Bardeen  and  Warren  Lewis  consider  that  "  the  myotomes 
play  no  part  whatever  in  the  origin  of  the  musculature  of  the  limbs." 
Moreover,  Lewis  states  that  "  the  idea  that  myotomes  play  a  r61e  in  the 
origin  of  the  muscles  of  the  head  must  be  abandoned."  A  radical  differ- 


D 


FIG.  108. — TRANSVERSE  SECTIONS  THROUGH  THE  MIDDLE  OF  CERTAIN  SOMITES  IN  SUCCESSIVELY  OLDER 
CHICK  EMBRYOS.  A,  B,  AND  C.,  THROUGH  ONE  OF  THEJJSECOND  PAIR  OF  SOMITES  IN  EMBRYOS  OF 
NINE,  FIFTEEN,  AND  TWENTY-FIVE  SEGMENTS  RESPECTIVELY;  D,  THROUGH  ONE  OF  THE  FORTY-FOURTH 
PAIR  IN  AN  EMBRYO  OF  FIFTY-TWO  SEGMENTS.  X  230.  (Williams.) 

ao.,  Aorta;  d,  dermatome;  m,  myotome;  m.  t.,  medullary  tube;  n,  notochord;  s,  sclerotome;  x,  angle  at  which 

the  myotome  develops. 

ence  in  the  source  of  smooth  and  striated  fibers  has  therefore  not  been 
demonstrated,  but  the  two  forms  of  muscle  develop  very  differently. 
The  myoblasts  which  produce  striated  muscle  are  found  in  the  midst 


I2O 


HISTOLOGY 


of  a  mesenchymal  or  connective  tissue  network,  thus  differing  from  the 
myoblasts  of  smooth  muscle.  The  latter  unite  with  one  another  through 
protoplasmic  or  fibrous  processes;  the  striated  fibers  are  bound  together 
by  connective  tissue  sheaths.  In  producing  striated  fibers,  the  myo- 
blasts become  greatly  elongated  cylindrical  structures,  with  rounded  or 
blunt  ends.  Although  according  to  Schafer  they  generally  do  not  exceed 
36mm.  in  length,  they  sometimes  measure  from  53-123  mm.  (Stohr); 
their  diameter  is  o.oi-o.i  mm.  During  the  growth  of  the  myoblast, 
mitotic  nuclear  division  takes  place  repeatedly,  producing  multi-nucleate 
cells;  and  in  the  adult  fibers,  a  further  multiplication  of  nuclei  through 
amitosis  has  been  reported.  Each  developing  myoblast  thus  acquires 
a  row  of  centrally  placed  nuclei,  imbedded  in  granular  protoplasm.  In 
the  outer  part  of  the  myoblasts  coarse  myofibrils  develop,  which,  as  seen 
in  cross  section,  form  an  encircling  ring  about  the  nuclei  and  axial  core 
of  protoplasm  (Fig.  109).  The  entire  myoblast  is  surrounded  by  a  mem- 
brane, to  the  formation  of  which  the  adjacent  mesenchyma  contributes. 


Capillaries 


Bundles  of  fibrils 
(Cohnheim's  areas) 


FIG.  109. — CROSS  SECTION  OF  MYOBLASTS 
AND  MESENCHYMAL  CELLS  FROM  AN 
i8-MM.  PIG. 


Connective  tissue 


mes.,  Mesenchymal  cell;  f.,  myofibiril;  n.,     FIG.  no. — CROSS  SECTION  OF  FOUR  MUSCLE  FIBERS  OF  THE 


nucleus  of  a  myoblast;  s.,  sarcolemma. 


HUMAN  VOCAL  MUSCLE.     X  590. 


The  group  of  cells  shown  in  Fig.  109  corresponds  with  a  portion  of  the 
myotome  in  Fig.  108,  D.  It  is  sectioned  in  the  same  plane,  but  represents 
a  later  stage.  In  the  adult,  such  an  area  of  tissue  as  shown  in  Fig.  109 
becomes  a  group  of  fibers  as  in  Fig.  no.  The  myoblasts  have  greatly 
enlarged,  and  their  protoplasm  is  filled  with  myofibrils  which  are  often 
arranged  in  "fields,"  known  as  Cohnheim's  areas.  These  fields  are  cross 
sections  of  longitudinal  bundles  of  fibrils  known  as  muscle  columns,  which 
Schafer  later  named  sarcostyles  (i.e.,  muscle  columns).  The  term  sarco- 
style  is,  however,  often  loosely  applied  to  the  separate  myofibrils.  It  has 
been  supposed  that  the  fibrils  in  a  column  arise  by  the  longitudinal  split- 
ting of  a  primitive  myofibril,  but  in  sections  it  often  appears  that  the  areas 
or  columns  are  due  to  shrinkage.  As  the  fibrils  multiply,  the  nuclei,  each 


SKELETAL    MUSCLE 


121 


surrounded  by  a  small  amount  of  granular  protoplasm,  migrate  to  the 
periphery  of  the  fiber  and  rest  just  beneath  the  connective  tissue  invest- 
ment. Occasionally  a  nucleus  is  found  which  has  not  reached  the  surface. 
Toward  the  end  of  the  muscle  fiber,  the  nuclei  are  numerous,  and  may 
retain  their  central  position.  The  growth  of  the  fiber  in  length  is  supposed 
to  occur  at  the  extremities. 

The  central  position  of  the  nuclei  in  myoblasts  in  pig  embryos  was  clearly  de- 
scribed by  Schwann,  in  the  second  part  of  his  treatise  which  established  the  cellular 
structure  of  animals  (1839).  He  believed,  however,  that  the  myoblasts  were  formed 
by  the  coalescence  of  primary  round  cells  arranged  in  a  row.  The  gradual  and  nearly 
complete  transformation  of  the  protoplasm  into  longitudinal  fibrils  was  correctly 
observed.  Schwann  found  that  the  secondary  cells,  or  mature  fibers,  were  completely 
enclosed  in  structureless  membranes,  which  were  clearly  seen  in  shrunken  fibers  (Cf. 
Fig.  in). 

Every  striated  muscle  fiber  is  completely  invested  by  a  membrane 
named  the  sarcolemma  (o-a/o£,  flesh;  Xe/A/xa,  husk  or  shell).  This  term 


VI 

...I, 


=  =  S  &  5 


B   S 


-"  *  ; 


'N  Sarcoplasm. 


FIG.  in. — STRIATED 
MUSCLE  FIBER  o  F 
FROG,  TEASED  APART 
i  N  WATER,  BEING 
TORN  AT  x,  AND 

SHOWING  THE  SARCO- 
LEMMA AT  S  AND  S1. 


Light  band.  Dark  band. 

FIG.  112.  -LONGITUDINAL  SECTIONS  OF  STRIATED  MUSCLE. 
A.,  Sketch  to  show  the  relation  between  the  cells  and  fibers 

according  to  Baldwin,    a.,  Fibrous  membrane;  b.,nucleus 

of  a  muscle  cell  in  vertical  section;  c.,  sarcolemma;  d., 

myofibrils  artificially  separated. 
B.,  Part  of  a  fiber  from  a  straight  muscle  of  the  eye  of  a  calf. 

X   1000.    The  nucleus  is  seen  in  surface  view;  the  sarco- 

plasm  contains  chondrioconta. 


was  introduced  by  Bowman  (Phil.  Trans.,  1840)  who  described  the  mem- 
brane as  "a  tubular  sheath  of  the  most  exquisite  delicacy,  investing  every 
fasciculus  (  or  fiber)  from  end  to  end,  and  isolating  its  fibrillae  from  all  the 
surrounding  structures."  He  confirms  Schwann's  statement  that  it  is 
not  a  fibrous  structure  derived  from  the  surrounding  connective  tissue,  and 
he  states  that  the  nuclei  of  the  muscle  come  to  lie  "at  or  near  the  surface 
but  within  the  sarcolemma."  He  adds,  however,  that  he  has  seen  similar 
cells  in  the  sarcolemma  itself.  Since  Bowman's  time  there  has  been 
prolonged  discussion  as  to  the  nature  of  this  membrane.  The  outer  por- 
tion, which  may  occasionally  contain  nuclei,  appears  to  be  of  connective 
tissue  origin,  and  is  comparable  with  a  basement  membrane.  The  inner 


122  HISTOLOGY 

part,  or  true  sarcolemma,  is  a  structureless  membrane  closely  applied  to 
the  surrounding  connective  tissue.  It  appears  to  be  much  more  definite 
than  any  membrane  which  invests  smooth  muscle  fibers,  to  which  the  term 
sarcolemma  has  been  extended  by  Heidenhain  and  others.  The  sarco- 
lemma of  striated  muscle,  however,  is  not  yet  thoroughly  understood. 
Although  the  muscle  cells  are  generally  said  to  be  within  it,  Baldwin  finds 
that  they  are  outside  of  the  sarcolemma,  between  it  and  the  fibrous  base- 
ment membrane  (Fig.  112,  A).  Accordingly  he  agrees  with  Apathy  in 
regarding  the  myofibrils  as  comparable  with  connective  tissue  fibers.  The 
possibility  that  the  myofibrils  are  intercellular  will  be  discussed  under 
cardiac  muscle. 

The  appearances  of  skeletal  muscle  which  have  caused  it  to  be  called 
striated  are  found  only  in  longitudinal  sections,  including  those  which  are 
obliquely  longitudinal.  It  is  then  seen  that  the  myofibrils,  which  run 
lengthwise,  are  composed  of  alternating  light  and  dark  portions,  and  that 
they  are  so  arranged  that  the  dark  parts  of  one  fibril  are  beside  the  dark 
parts  of  the  adjacent  fibrils.  As  a  result  of  the  close  crowding  of  the  fibrils, 
alternating  light  and  dark  transverse  bands  appear  to  pass  from  one  side 
of  the  fiber  to  the  other,  and  these  are  the  striations.  They  are  shown  in 
Fig.  112,  A  and  B  (at  the  right  of  A,  the  fibrils  are  represented  as  artificially 
frayed  apart). 

Bowman  (1840)  stated  that  "a  decisive  characteristic  of  voluntary  muscle  consists 
in  the  existence  of  alternate  light  and  dark  lines,  taking  a  direction  across  the  fasciculi." 

He  added  that  Leeuwenhoek  had  described 
the  striae  repeatedly,  believing  in  the  earlier 
years  of  his  inquiry  that  they  were  circular 
bands  around  the  fibrils,  but  later  regarding 
them  as  of  spiral  arrangement,  comparable 
with  an  elastic  coil  of  wire,  and  in  some  way 
capable  of  retraction.  Bowman  recognized 
that  they  were  caused  by  the  "  coaptation  of 
the  markings  of  neighboring  nbrillae."  He 

found  ^^  the  muscle  fibers  can  readily  be  split 

Bowman.)  into  longitudinal  nbrillae  with  transverse  mark- 

ings,  but   that  "in  other  cases  their  natural 

cleavage  is  into  discs,  and  in  all  instances  these  discs  exist  quite  as  unequivocally  as 
the  nbrillae  themselves."  The  discs  are  produced  when  the  ends  of  a  muscle  fiber 
are  pulled  apart  (Fig.  113).  Bowman  regarded  each  disc  as  a  plate  of  agglutinated 
segments,  receiving  a  single  segment  from  every  fibrilla  which  crossed  it.  These  seg- 
ments he  named  sarcous  elements;  they  are  united  endwise  to  form  the  myofibrils  and 
crosswise  to  form  the  discs.  Usually  the  longitudinal  cohesion  is  much  greater  than 
the  lateral,  and  in  the  wing  muscles  of  insects,  according  to  Schafer,  the  fiber  "never, 
under  any  circumstances,  cleaves  across  into  discs." 

The  finer  structure  of  the  fibrils  is  illustrated  in  the  diagram,  Fig.  114, 
which  represents  a  part  of  seven  myofibrils,  including  three  dark  bands 


SKELETAL   MUSCLE 


123 


and  portions  of  four  light  bands.  Under  polarized  light  the  dark  bands 
are  doubly  refractive  or  anisotropic,  and  the  light  ones  are  singly  refractive 
or  isotropic.  Following  Rollett's  suggestion,  the  striations  are  often 
designated  by  letters.  The  dark  band  is  called  Q  (an  abbreviation  for 
Querscheibe,  or  transverse  band)  and  the  light  band  is  called  J  (applied  by 
Rollett  to  a  subdivision  of  the  isotropic  layer).  The  light  band  is  bisected 
by  the  ground  membrane,  or  Krause's  membrane,  which  appears  as  a  very 


FIG.  114.  — DIAGRAM  OF  MUSCLE  STRIATIONS.    (After  Heidenhain.) 

The  fibrils  consist  of  alternating  dark  bands,  Q,  and  light  bands,  J.  J.  is  traversed  by  the  ground  mem- 
brane Z,  and  Q  by  the  median  membrane  M.  In  the  right  of  the  three  muscle  segments  shown  in 
the  figure,  the  bands,  N,  have  been  drawn. 

slender  dark  line,  Z  (Zwischenscheibe,  or  intermediate  disc) .  The  lines 
Z  are  believed  to  represent  continuous  membranes  which  divide  the  muscle 
fiber  *into  compartments  called  muscle  segments,  or  sar comer es.  At  the 
sides  of  the  fiber,  Krause's  membranes  join  the  sarcolemma,  which  bulges 
between  them  when  the  fibers  are  contracted  (Fig.  112,  A).  Between 
Z  and  (?,  in  the  highly  developed  striated  muscles  of  inserts,  a  band  ./V 
has  been  described  (Nebenscheibe,  or  accessory  band).  The  dark  band 


FIG.    115. — FIBRILS  OF  THE  WING-MUSCLES  OF  A  WASP;  THE  UPPER  ONE  CONTRACTED;  THE  MIDDLE  ONE 
STRETCHED;  AND  THE  LOWEST  ONE  UNCONTRACTED.     X  2000.    (Schafer.) 

Q  becomes  gradually  lighter  toward  its  central  part  (thus  forming  h  or 
Qti),  and  in  its  central  part  it  is  sometimes  seen  to  be  crossed  by  Hensen's 
median  membrane,  M  (Mittelscheibe) .  The  latter  is  believed  to  be  similar 
to  Krause's  membrane,  but  more  delicate.  Like  the  other  bands  it  may 
appear  dark  or  light  according  to  the  focus.  In  the  muscle  fibrils  shown 
in  Fig.  115,  the  bands  Q,  J,  and  Z  may  be  readily  identified;  M  appears 
as  a  rather  broad  white  line  which  may  include  Qh. 


124  HISTOLOGY 

Between  the  myofibrils  and  completely  surrounding  them  is  the  sar co- 
plasm,  which  is  a  fluid  substance  containing  interstitial  granules,  fat  drop- 
lets, and  glycogen.  It  differs  from  the  protoplasm  of  the  muscle  cells 
which  is  found  about  the  nuclei,  and  which  is  cut  off  from  the  sarcoplasm, 
according  to  Baldwin,  by  the  sarcolemma.  The  granules  have  been  care- 
fully studied  by  Bullard  (Amer.  Journ.  Anat.,  1912,  vol.  14,  pp.  1-46)  who 
discusses  their  staining  reactions  and  probable  composition.  The  sig- 
nificance of  the  interstitial  granules  could  not  be  determined.  The  fat 
droplets  are  regarded  as  reserved  food  material,  and  they  vary  in  abun- 
dance according  to  the  quantity  of  fat  in  the  food.  Schafer  has  found  no 
evidence  that  the  isolated  sarcoplasm  of  insect  muscles  is  contractile,  but 
he  readily  observed  the  contractility  of  isolated  myofibrils.  Moreover  the 
activity  of  certain  muscles  in  living  embryos  begins  soon  after  the  fibrils 
are  differentiated. 

In  the  process  of  contraction,  according  to  Schafer,  the  hyaline  sub- 
stance of  the  myofibril  passes  from  the  light  segment  /  into  the  dark  seg- 
ment Q,  so  that  each  sarcomere  becomes  short  and  broad.  He  refers  to 
the  photograph  of  the  lowest  fibril  in  Fig,  115  as  showing  that  the  dark 
substance  is  porous  (note  the  end  of  the  fiber  toward  the  right).  The 
sarcolemma  bulges  between  the  successive  Krause's  membranes,  which  are 
brought  closer  together  (Fig.  112,  A),  and  the  length  of  each  sarcomere  is 
greatly  reduced.  The  dark  band  Q  may  become  light  through  the  accumu- 
lation of  hyaline  substance  within  it,  and  the  shortened  and  condensed  / 
may  become  quite  dark,  causing  a  reversal  of  the  original  color  relations. 
The  sarcoplasm  is  said  to  be  forced  from  between  the  dilated  myofibrils  in 
Q,  into  /.  Others  consider  that  contraction  is  due  to  a  passage  of  fluid 
from  the  sarcoplasm  into  the  myofibrils,  and  that  the  beaded  form  which 
the  myofibrils  often  present,  results  from  an  intake  of  fluid  through  the 
ultra-microscopic  membranes  which  are  supposed  to  surround  them.  The 
latter  interpretation  is  defended  by  Meigs  (Zeitschr.  f.  allg.  Physibl.,  1908, 
vol.  8,  pp.  81-120),  and  vigorously  attacked  by  Schafer  (Quart.  Journ. 
Exp.  Physiol.,  1910,  vol.  3,  pp.  63-74).  The  older  theories  of  contraction 
and  the  numerous  papers  on  the  finer  structure  of  striated  muscle  are 
admirably  reviewed  by  Heidenhain  (Anat.  Hefte,  Abth.  2,  1899,  vol.  8,  pp. 
i-m). 

Adult  muscle  is  composed  of  such  fibers  as  have  been  described  in  the 
preceding  paragraphs.  They  are  arranged  in  compact  bundles,  shown  in 
cross  section  in  Fig.  116.  Around  all  the  larger  muscles  there  is  a  connec- 
tive tissue  sheath,  or  external  perimysium,  which  extends  into  the  muscle  in 
the  form  of  septa,  thus  subdividing  it  into  bundles  or  fasciculi.  These 
septa  constitute  the  internal  perimysium,  and  the  connective  tissue  ex- 
tends from  them  around  the  individual  muscle  fibers,  blending  with  the 
sarcolemma.  In  the  connective  tissue  of  the  diaphragm,  elastic  fibers  are 


SKELETAL   MUSCLE 


125 


abundant;  but  the  muscles  of  the  extremities  are  poor  in  elastic  tissue, 
containing  only  fine,  chiefly  longitudinal  fibers,  found  especially  in  the 
perimysium  externum. 

Cross  sections  of  striated  muscle  fibers  are  readily  recognized.  They 
have  rounded-polygonal  outlines  formed  by  the  sarcolemma  and  fibrous 
membrane,  within  which  are  the  myofibrils,  often  shrunken  from  the 
membrane.  The  fibrils  stain  intensely  with  eosin.  They  appear  as  coarse 
granules,  but  their  rod-like  form  becomes  evident  as  they  are  followed  up 
and  down  by  changing  the  focus.  The  shifting  picture  thus  presented  is 
quite  characteristic.  Some  fibers  stain  more  darkly  than  others,  owing  to 
the  varying  abundance  of  sarcoplasmic  granules. 


External  perimysium. 


Muscle  bundles. 


Internal  perimysium. 


Cross  section  of  artery. 
Muscle  spindle. 

Cross  section  of  nerve. 
FIG.  116. — FROM  A  CROSS  SECTION  OF  THE  OMOHYOID  MUSCLE  OF  MAN.     X  60. 

In  many  animals,  as  in  the  rabbit,  two  sorts  of  striated  muscles  may  be  recognized 
— red  muscle  (e.g.,  the  M.  semitendinosus  and  M.  soleus);  and  pale  or  white  muscle 
(e.g.,  the  M.  adductor  maghus).  Correspondingly  there  are  two  sorts  of  fibers. 
First,  there  are  dark  fibers  with  abundant  sarcoplasm,  well  defined  longitudinal 
striation,  and  poorly  developed  transverse  markings,  having  in  general  a  small 
diameter;  these  occur  in  red  muscles.  Secondly,  there  are  pale  fibers,  with  less  sar- 
coplasm and  better  defined  transverse  striations,  having  a  greater  diameter.  These 
are  the  more  highly  differentiated  fibers.  Although  in  some  animals  these  two  sorts 
of  fibers  are  found  in  separate  muscles,  in  others,  as  in  man,  they  are  mingled  in 
single  muscles.  In  general  the  most  constantly  active  muscles  (cardiac,  ocular, 
masticatory  and  respiratory)  contain  the  most  fibers  with  abundant  sarcoplasm. 
The  muscles  having  many  fibers  with  scanty  sarcoplasm  contract  more  quickly  but 
are  exhausted  sooner. 


126  HISTOLOGY 

The  size  of  the  muscle  fibers  is  subject  to  considerable  variation.  They 
are  said  to  enlarge  at  a  uniform  rate  throughout  the  body  until  birth,  when 
their  diameter  is  about  twice  as  great  as  in  embryos  of  four  months.  After 
birth  the  fibers  of  certain  muscles  become  much  coarser  than  those  in 
others.  Thus  the  gluteal  muscles  have  large  fibers  (av.  diam.  87.5^) 
and  the  ocular  muscles  have  small  ones  (av.  diam.  17.5  /A),  as  determined  by 
Halban  (Anat.  Hefte,  Abth.  i,  1894,  vol.  3,  pp.  267-308).  He  finds  that 
the  diameter  of  the  adult  fibers  in  general  is  about  five  times  greater  than 
at  birth.  As  a  result  of  exercise  the  diameter  of  muscle  fibers  in  rats  may 
show  an  average  increase  of  25%  according  to  Morpurgo  (Arch.  f.  path. 
Anat.,  1897,  v°l-  IS°j  PP-  522~554)-  He  states  that  the  enlargement  of  the 
muscle  takes  place  without  an  increase  in  the  number  of  its  fibers,  but  merely 
through  the  thickening  of  existing  elements.  'The  fibers  which  grow  most 
are  those  which  originally  were  thinnest,  and  which  act  as  a  reserve 
material  with  great  capacity  for  growth.  The  enlargement  of  fully  formed 
fibers  apparently  takes  place  through  an  increase  in  the  sarcoplasm,  with- 


Transition  zone. 


Nlfcleus        tendon.  Q   Z 

FIG.  117. — BRANCHED   STRI-  FIG.  118. — LONGITUDINAL  SECTION  OF  A  PART  OF  A  MUSCLE 

ATED  MUSCLE  FIBER  FROM  FIBER  FROM  A  HUMAN  INTERNAL  INTERCOSTAL  MUSCLE,  SHOW- 

THE  TONGUE  OF  A  FROG.  ING  ITS  TRANSITION  TO  TENDON.     X  750. 


out  multiplication  or  thickening  of  the  fibrils.  After  injury  striated  mus- 
cle gives  slight  evidence  of  regeneration,  but  it  has  been  thought  that 
latent  myoblasts  may  become  active.  A  proliferation  of  nuclei  toward 
the  injured  ends  of  the  muscle  fibers  has  been  recorded,  but  repair  is  chiefly 
through  the  production  of  connective  tissue. 

Longitudinal  sections  of  skeletal  muscles  may  be  easily  recognized 
by  the  presence  of  unbranched  striated  fibers,  bounded  by  well-defined 
membranes,  associated  with  which  are  the  flattened  peripheral  nuclei.  The 
striations  Q  and  /  are  visible  under  low  magnification.  In  a  few  situa- 
tions, striated  muscle  fibers  branch  (Fig.  117).  Branching  has  been  re- 
ported toward  the  place  where  the  muscle  fibers  of  the  tongue  are  inserted 
into  the  mucous  membrane,  and  where  the  facial  muscles  end  in  the  sub- 
cutaneous tissue.  The  way  in  which  the  fibers  connect  with  tendon  has 


SKELETAL   MUSCLE  127 

been  studied  with  conflicting  results.  Schultze  finds  that  at  the  end  of 
the  muscle  fiber  the  myofibrils  are  no  longer  differentiated  into  light  and 
dark  bands,  but  pass  directly  into  the  tendon  fibrils,  with  which  they  are 
continuous  (Fig.  118).  "  Muscle  fibrils  and  tendon  fibrils  are  parts  of  a 
single  structure."  (Arch.  f.  mikr.  Anat.,.  1912,  vol.  79,  pp.  307-331).  But 
Baldwin  finds  that  the  ends  of  the  muscle  fibers  are  primarily  conical  and 
are  covered  with  sarcolemma;  and  the  tendon  fibrils  connect  with  the 
sarcolemma  at  the  apices  of  the  cones.  The  processes  of  sarcolemma  are 
thus  primarily  " dovetailed"  into  the  tendon.  Secondarily  the  cones 
may  blend  to  form  a  thickened  flat  layer  to  which  perichondrial  or  perios- 
teal  fibers  are  attached.  In  no  case  is  the  sarcolemma  penetrated  by 
muscle  fibrils  or  tendon  fibrils,  and  therefore  there  is  no  continuity  between 
them  (Morph.  Jahr.,  1912,  vol.  45,  pp.  249-266).  Thus  Baldwin  defends 
the  generally  accepted  opinion. 

Muscles  are  abundantly  supplied  with  vessels  and  nerves,  which  are 
imbedded  in  the  perimysium.  The  lymphatic  vessels  end  in  the  septa 
without  extending  among  the  individual  muscle  fibers;  but  the  blood 

Vessels,      through      Capillary  -Muscle  fiber.        Connective  tissue. 

branches,  continue  further  and 

run   between    adjacent    fibers,        Connective  tissue. 

thus    forming    a    plexus    with 

elongated    rectangular  meshes. 

The  nerves   are  chiefly  motor, 

and  a  branch  ends  in  contact 

with    every    muscle    fiber,    to 

Which  it  transmits  the  impulse  cross  section'  Muscle  fibers  Nucleus  Nucleus  of  the 
ts^-~  -^4-  ^4-'^~  TV/T  ,~^  1  of  nerve.  of  the  of  the  sarcolemma. 

tOr    Contraction.        MUSCleS    alSO  spindle,     perimysium. 

contain  sensory  nerves,  having  FlG-  II0- — THE  MUSCLE  SPINDLE  SHOWN  IN  FIG.  n6. 
"free  endings"  and  probably 

terminating  also  around  the  muscle  spindles.  The  spindles  are  slender 
bundles  of  poorly  developed  fibers,  generally^  situated  near  the  septa 
formed  by  the  internal  perimysium,  as  seen  in  Figs.  116  and  119.  All 
the  muscle  spindles  are  formed  during  embryonic  life,  and  their  abun- 
dance and  distribution  in  the  various  muscles  in  embryos  have  been 
studied  by  Gregor  (Arch.  f.  Anat.  u.  Entw.,  1904,  pp.  112-194).  They 
have  not  been  found  in  all  muscles,  and  in  certain  muscles  they  are 
regularly  more  numerous  than  in  others.  Thus  they  have  been  reported 
as  absent  from  the  muscles  of  the  eye,  face,  pharynx,  small  muscles  of 
the  larynx,  the  Mm.  ischiocavernosus  and  bulbocavernosus,  and  certain 
others,  including  a  large  part  of  the  diaphragm.  They  are  numerous  in 
the  distal  muscles  of  the  limbs,  and  in  certain  muscles  of  the  neck.  The 
finer  structure  of  the  nerve  terminations,  both  motor  and  sensory,  will  be 
considered  with  the  nervous  system. 


128 


HISTOLOGY 


CARDIAC  MUSCLE. 

A  portion  of  the  mesenchymal  syncytium  from  which  cardiac  muscle 
develops  is  shown  in  Fig.  120.  Its  nuclei  are  found  in  the  axial  part  of  the 
protoplasmic  strands,  at  varying  intervals  from  one  another.  Peripherally 
a  few  myofibrils  have  developed  from  the  chondrioconta,  or  protoplasmic 
granules,  and  these  fibrils  extend  for  considerable  distances  through  the 
syncytium  regardless  of  cell  areas.  They  multiply  rapidly,  and  form  a 
peripheral  layer  of  fibrils  surrounding  the  central  nuclei  and  axial  proto- 
plasm. Thus  as  seen  in  cross  section,  the  strands  of  cardiac  syncytium 

and  the  myoblasts  of  skeletal  muscle 
resemble  one  another.  The  fibrils 
exhibit  alternating  dark  and  light 
bands  which  are  arranged  as  in 
skeletal  muscle,  and  ground  mem- 
branes (Z)  develop  across  the  fibers, 
bisecting  the  light  bands  (/).  The 
striations,  however,  are  not  as  regular 
and  as  highly  developed  as  in 
skeletal  muscle.  At  the  periphery 
of  the  fibers  there  is  a  sarcolemma, 
which  is  thinner  than  that  of  skeletal 
muscle,  and  was  formerly  overlooked. 
In  early  stages  the  muscle  fibers  in 
many  places  rest  close  against  the 
endothelium  of  blood  vessels;  later 
they  are  surrounded  by  more  or  less 
connective  tissue. 

In  the  adult  .the  cardiac  muscle  fibers  anastomose  freely,  thus  retaining 
their  original  syncytial  arrangement  (Fig.  121).  They  do  not,  however, 
form  an  irregular  network,  but  are  arranged  in  layers,  in  which  the  fibers 
tend  to  be  parallel.  Thus  they  are  cut  longitudinally  in  Fig.  121  and 
transversely  in  Fig.  172  (p.  179).  The  nuclei  retain  their  central  position. 
They  are  elliptical  bodies  with  a  conical  mass  of  protoplasm  at  either  pole. 
This  protoplasm,  as  in  smooth  muscle,  occupies  the  interval  left  between 
the  fibrils  as  they  diverge  to  pass  by  the  nucleus.  It  is  granular,  and 
frequently  contains  brown  pigment. 

According  to  Apathy  (Biol.  Centralbl.,  1888,  vol.  7)  "the  contractile  substance 
is  a  product  of  the  muscle  cell  and  the  muscle  cell  is  represented  by  the  nucleus  and 
surrounding  area  of  protoplasm."  "The  myofibrils  of  the  contractile  substance  are 
the  histogenetic  homologues  of  connective  tissue  fibrils,  however  much  they  may 
differ  from  them ' chemically  or  functionally."  Baldwin  has  recently  advanced  a 
similar  interpretation.  He  finds  that  the  sarcoplasm  between  the  fibrils  differs  from 
the  protoplasm  around  the  nucleus.  Moreover  he  states  that  the  perinuclear  proto- 


r"  FIG.  120. — CARDIAC  MUSCLE  FROM  A  DUCK 
EMBRYO  OF  THREE  DAYS.  (M.  Heidenhain,  from 
McMurrich's  "Embryology.") 


CARDIAC   MUSCLE 


129 


plasm,  in  both  skeletal  and  cardiac  muscle,  is  separated  by  the  sarcolemma  from  the 
myofibrils  and  sarcoplasm  (Fig.  112,  A).  In  regard  to  smooth  muscle,  however, 
Baldwin  merely  notes  that  it  should  be  reviewed  in  the  light  of  these  facts.  The 
existence  of  a  membrane  around  the  nu- 

,  ,  Al          Nucleus.  Sarcoplasm.     Fibrils.         Lateral  branch 

cleus  and  granular  protoplasm  at  its  pples 
would  place  smooth  muscle  in  the  same 
category,  and  make  the  fibrils  extracellular. 
With  muscle,  therefore,  as  with  connec- 
tive tissue,  the  distinction  between  intra- 
cellular  and  extracellular  appears  to  be 
arbitrary  and  conventional.  It  is  interest- 
ing to  note  that  the  extrusion  of  the  nuclei 
from  the  precartilage  matrix  to  its  surface, 
as  described  by  Mall,  may  be  comparable 
with  the  passage  of  the  nuclei  from  the  cen- 
ter to  the  surface  of  skeletal  muscle  fibers. 
Baldwin's  papers  are  found  in  the  Zeitschr. 
f.  allg.  Physiol.,  1912,  vol.  14,  pp.  130-160, 
and,  as  regards  cardiac  muscle,  in  the 
Anat.  Anz.,  1912,  vol.  42,  pp.  177-181. 

A  feature  of  cardiac  muscle  which 
is  unlike  anything  observed  in  smooth 
or  skeletal  fibers  is  the  presence  of  in- 
tercalated discs.  These  are  transverse 
lines  across  the  fibers,  which  were 
formerly  interpreted  as  cell  bounda- 
ries, and  some  authorities  still  regard 
them  as  such.  In  the  guinea-pig 

Jordan  and  Steele  find  that  they  firstappear  during  the  week  before  birth. 
Thus  they  are  late  in  development,  and  they  are  relatively  less  abundant 

and  simpler  in  the  young  than  in  adults  (Amer. 
Journ.  Anat,  1912,  vol.  13,  pp.  151-173).  If 
the  cardiac  syncytium  ultimately  became  re- 
solved into  cells,  it  would  resemble  certain  other 
syncytia  in  this  respect;  and  cardiac  muscle  can 
be  broken  up  into  cell-like  blocks,  apparently 
along  these  discs.  However,  the  discs  occur  at 
variable  distances  from  one  another,  and  very 
frequently  they  mark  off  non-nucleated  por- 
tions of  the  syncytium.  As  many  as  four  of 
them  may  extend  partly  across  a  single  nucleus, 
as  shown  by  Jordan  and  Steele,  indicating  that 
they  are  peripheral  modifications  of  the 
myofibrils,  and  cannot  be  regarded  as  cell  walls.  Heidenhain  (Anat. 
Anz.,  1901,  vol.  20,  pp.  33-78)  pictures  them  as  always  connected  on  one 

9 


x       Conn,  tissue.     Capillaries. 

PIG.  121. — LONGITUDINAL  SECTION  OF  A  PAPIL- 
LARY MUSCLE  FROM  THE  HUMAN  HEART.  X  240. 
The  transverse  lines  (x)  are  partly  light  (where  the 

fiber  has  broken)    and  partly  dark  (intercalated 

discs) 


FIG.  122. — INTERCALATED  Disc  (d) 
FROM  HUMAN  CARDIAC  MUSCLE, 
STAINED  WITH  THIAZIN  RED  AND 
TOLUIDIN  BLUE.  Z,  Krause's 
membrane.  (Heidenhain.) 


130 


HISTOLOGY 


side  with  a  ground  membrane  Z  (Fig.  122),  and  states  that  they  are  some- 
what narrower  than  a  sarcomere  (i.e.,  the  distance  between  two  successive 
ground  membranes) .  He  regards  them  as  the  places  where  new  sarcomeres 
form,  thus  providing  for  the  growth  of  the  heart.  Jordan  and  Steele, 
among  others,  consider  that  they  are  places  where  individual  fibrils  are 
contracted,  and  the  fact  that  they  are  shorter  than  adjacent  sarcomeres 
favors  this  interpretation.  The  discs  may  extend  straight  across  the  fiber, 
but  frequently  they  are  broken  into  " steps"  as  shown  in  the  figure. 
•  There  are,  therefore,  three  peculiarities  of  cardiac  muscle  through  which 
it  differs  conspicuously  from  skeletal  muscle,  namely,  its  anastomosing 
fibers,  central  nuclei,  and  intercalated  discs. 

NERVOUS  TISSUE. 

General  features.  In  nervous  tissue  the  protoplasmic  functions  of  irri- 
tability and  conductivity  attain  their  highest  development.  Irritability 
is  that  property  which  enables  the  cell  to  react  to  various  stimuli,  such  as 
pressure  or  light;  and  through  conductivity  the  effects  of  stimulation  are 
transmitted  to  distant  parts  of  the  cell,  or  to  adjacent  cells.  In  all  animals 
the  cells  of  the  outer  or  ectodermal  layer  are  those  most  exposed  to  stimu- 
lation, and  the  ectoderm  accordingly  gives  rise  to  the  entire  nervous  system. 
In  some  animals  all  the  ectodermal  cells  have  been  described  as  equally 
responsive  to  stimulation,  and  the  name  " sensory  layer'7  has  been  applied 
to  the  ectoderm  as  a  whole.  Usually,  however,  the  sensory  cells  become 
specialized  in  definite  and  limited  areas  of  the  ectoderm.  M.  Schultze 
(1862)  showed  that  the  sensory  cells  of  the  nose  and  eye  are  epithelial 
elements,  the  bases  of  which  are  prolonged  into  filaments  which  serve  as 
nerves  to  convey-  sensation.  He  taught  that  the  specific  functions  of  the 
sense  organs  depend  on  their  respective  epithelial  cells,  which  accordingly 
may  be  designated  as  olfactory,  gustatory,  auditory  or  visual  cells. 

Not  only  does  the  ectoderm  produce  sensory  neuro-epithelial  cells,  the 
nucleated  bodies  of  which  remain  in  the  epithelium,  but  it  gives  rise  to  more 
deeply  placed  nerve  cells,  which  connect  with  the  epithelial  cells  and  place 
them  in  communication  with  the  muscles.  In  simple  forms  of  animals  this 
connection  is  very  direct,  and  the  response  of  the  muscle  to  epithelial 
stimulation  is  quite  automatic.  In  the  higher  animals  there  are  both 
direct  and  indirect  paths  from  the  sensory  endings  to  the  muscles,  and  mus- 
cular action  may  be  inhibited  or  initiated  by  certain  of  the  centrally 
placed  nerve  cells. 

The  centrally  placed  cells  in  vertebrates  constitute  the  spinal  cord  and 
brain,  which  together  form  the  central  nervous  system.  The  bundles  of 
fibers  which  convey  impulses  to  and  from  the  central  nervous  system,  to- 
gether wkh  the  cells  associated  with  them,  constitute  the  peripheral  nervous 
system. 


NERVOUS    TISSUE  131 

In  the  olfactory  epithelium  of  vertebrates  there  are  neuro-epithelial 
cells  which  send  fibers  directly  into  the  central  nervous  system,  but  in 
other  cases  the  nucleated  bodies  of  the  sensory  cells  are  not  found  in  the 
epithelium.  They  occur  in  circumscribed  masses  or  ganglia,  from  which 
fibers  extend  both  into  the  central  nervous  system,  and  outward  to  various 
sensory  structures,  where  they  terminate  in  contact  with  cells  which  stimu- 
late them.  Thus  the  stimulus  which  gives  rise  to  a  tactile  sensation  is 
received  by  the  terminal  ramifications  of  a  nerve  fiber  in  the  skin.  The 
stimulus  is  conveyed  along  this  fiber  (Fig.  123,  a),  through  the  spinal 
ganglion  (6),  into  the  spinal  cord,  where  it  produces  several  branches  (at  c). 
One  of  these  branches  passes  to  a  motor  cell,  d,  to  which,  through  contact,  it 


FIG.  123. — DIAGRAM  OF  THE  SPINAL  CORD  SHOWING  A  SENSORY  FIBER,  a;  A  MOTOR  FIBER,  e;  AND  THE 
FIBERS  WHICH  CONNECT  THEM  WITH  EACH  OTHER  AND  WITH  THE  BRAIN. 

transmits  its  stimulus.  The  motor  cell  sends  a  fiber  outward  (e)  to  termi- 
nate in  contact  with  a  striated  muscle,  which  is  thereby  stimulated  so  that 
it  contracts.  This  direct  path  from  the  sensory  ending  to  the  muscle,  pro- 
vides for  reflex  or  unconscious  action,  such  as  is  taken  when  the  hand  is 
suddenly  withdrawn  from  a  painful  contact.  In  such  a  case  a  considerable 
group  of  muscles  may  contract  together,  since  the  sensory  fiber  sends 
branches  up  and  down  the  cord  (/"),  and  these  in  turn  give  off  collateral 
branches  which  pass  to  motor  cells  at  different  levels. 

The  cell  which  conveys  the  tactile  sensation  from  the  skin  to  the  spinal 
cord  gives  rise  to  branches  which  terminate  in  contact  with  other  cells  in 
the  spinal  cord,  as  shown  in  Fig.  123,  g.  From  these  cells  processes  cross 
to  the  opposite  side  of  the  cord  and  pass  up  to  the  brain  (h\  where  they 
connect  with  nerve  cells  through  which  the  sensations  become  conscious. 
These  brain  cells  presumably  become  permanently  modified  by  the  sensa- 
tions which  they  receive,  so  that  they  store  experiences.  As  a  result  of  the 
sensation  transmitted  from  the  skin,  certain  cells  in  the  brain  may  send 
stimuli  downward  to  the  motor  cells  of  the  cord,  which  then  cause  the 


132 


HISTOLOGY 


muscles  to  act  voluntarily.  The  descending  fiber  crosses  to  the  opposite 
side  during  its  descent,  and  occupies  the  position  in  the  cord  shown  in  Fig. 
123,  i.  A  branch  is  shown  passing  to  the  motor  cell,  d. 

From  this  sketch  of  the  constitution  of  the  nervous  system,  it  is  seen 
that  it  consists  essentially  of  cells,  made  up  of  cell  bodies  and  of  fibers;  the 
fibers  are  prolongations  of  the  cell  bodies.  The  cells  are  sensory,  or  afferent, 
conveying  impulses  toward  the  central  nervous  system;  and  motor,  or 
efferent,  conveying  impulses  away  from  the  central  system.  Within  the 
cord  these  cells  connect  with  others,  forming  ascending  and  descending 
tracts,  or  bundles  of  fibers  passing  toward  the  brain  and  away  from  it, 
respectively.  Fibers  which  serve  to  connect  different  levels  of  the  cord 
with  one  another  are  known  as  association  fibers;  those  which  connect 
the  opposite  sides  are  commissural  fibers. 

Certain  features  in  the  development  of  the  nervous  system  in  lower  animals,  of 
interest  in  connection  with  the  mammalian  nervous  system,  are  shown  diagram- 
matically  in  Fig.  124.  In  sponges,  according  to  Parker,  there  is  no  nervous  tissue  of 
any  sort,  but  beneath  the  thin  epithelium  he  finds  elongated  contractile  cells  which 
"resemble  primitive  smooth  muscle  fibers"  (Fig.  124,  A).  They  have  been  regarded 
as  modified  epithelial  cells.  Parker  finds  that  they  are  stimulated  directly,  as  a  result 


b. 


FIG.  124. — A,  DIAGRAM  OF  THE  MUSCULAR  MECHANISM  IN  A  SPONGE.  (Parker.)  B,  DIAGRAM  OF  THE 
NEURO-MUSCULAR  MECHANISM  IN  A  MEDUSA.  (Parker,  after  Hertwig.)  C,  DIAGRAM  OF  THE 
VENTRAL  NERVOUS  CHAIN  (c)  AND  ADJACENT  STRUCTURES  IN  AN  EARTHWORM.  (Parker,  after 
Retzius.) 

a,  Longitudinal  muscle;  b,  motor  fiber;  d,  sensory  fiber;  e,  ^epithelium  on  the  under  surface  of  the 
body,  containing  neuro-epithelial  cells. 

of  changes  in  the  sea-water,  so  that  they  slowly  contract  and  close  the  orifices  around 
which  they  are  situated.  Since  the  sponges  are  lower  than  any  animals  which  are 
known  to  have  nerve  cells,  Parker  concludes  that  muscular  tissue  arose  independently 
of  nervous  tissue,  and  is  the  more  primitive  (Journ.  Exp.  Zool.,  1910,  vol.  8,  pp.  1-41). 

In  the  medusae,  neuro-epithelial  cells,  nerve  cells,  and  both  smooth  and  striated 
muscle  fibers  are  present.  According  to  Oskar  and  Richard  Hertwig,  the  muscle 
cells  are  derived  from  the  deep  part  of  the  ectodermal  epithelium,  and  from  the 
first  they  are  connected  with  nerve  cells  or  neuro-epithelial  cells  (Fig.  124,  B).  In 
other  words,  in  the  medusae  muscle  and  nerve  develop  in  primary  communication 
with  one  another  (Das  Nervensystem  der  Medusen,  Leipzig,  1878). 

In  the  earthworm  (Fig.  124,  C)  neuro-epithelial  cells  in  the  ventral  body  wall 
send  fibers  to  a  cord  of  nervous  tissue  which  constitutes  a  central  nervous  system. 
From  cells  in  this  cord,  processes  extend  to  the  muscles,  as  shown  in  the  diagram. 
Thus  the  neuro-epithelial  cell  does  not  stimulate  the  muscle  directly;  it  conveys  an 
impulse  to  the  motor  cell  which  in  turn  acts  upon  the  muscle.  In  addition  to  the 


NERVOUS    TISSUE 


133 


cells  shown  in  the  diagram  the  cord  contains  ramifying  association  and  commissural 
cells.  Thus  stimulation  at  one  point  on  the  surface  of  the  animal  may  cause 
coordinated  muscular  contractions  in  different  parts  of  the  body.  As  Retzius  has 
pointed  out,  if  the  neuro-epithelial  cells  should  withdraw  into  the  interior  of  the 
animal,  leaving  their  branching  process  in  the  epidermis,  the  conditions  in  verte- 
brates would  be  closely  paralleled. 

The  development  and  structure  of  the  central  nervous  system  and  the 
sense  organs  will  be  considered  in  a  later  chapter.  The  following  account 
deals  first  with  the  development  of  the  spinal  nerves,  the  spinal  sympathetic 
system,  and  the  cerebral  nerves;  and  secondly,  with  the  adult  structure 
of  these  parts,  including  the  ganglia,  nerve  trunks,  and  nerve  endings. 


DEVELOPMENT   OF   THE    SPINAL  NERVES. 

The  formation  of  the  medullary  groove  (or  neural  groove)  as  a  longi- 
tudinal trough  in  the  ectoderm,  and  its  conversion  into  the  medullary  tube 


A 


sp-g 
vr 


•  c.c 


FIG.  125.— THE  DEVELOPMENT  OF  THE  NERVOUS  SYSTEM  AS  SEEN  IN  CROSS  SECTIONS  OF  RABBIT  EMBRYOS: 
A,  7^  DAYS;  B,  8*  DAYS;  C,  9  DAYS;  D,  ioi  DAYS;  E,  14  DAYS. 

c.  c.,  Central  cavity;  d.  r.,  dorsal  root;  d.  ra.,  dorsal  ramus;  ep.,  ependymal  layer;  g.  c.,  ganglion  cells; 
g.  1.,  gray  layer;  m.  g.,  medullary  groove;  m.  t.,  medullary  tube;  o.  b.,  oval  bundle;  s.  g.,  sympathetic 
ganglion;  sp.  g.,  spinal  ganglion;  s.  ra.,  sympathetic  ramus;  v.  r.,  ventral  root;  v.  ra.,  ventral  ramus; 
w.  1.,  white  layer. 

by  the  coalescence  of  its  dorsal  edges,  have  been  described  in  a  previous 
section  (p.  37).  The  anterior  part  of  the  tube  expands  to  form  the  brain; 
the  posterior  part  becomes  the  relatively  slender  spinal  cord. 

At  about  the  time  when  the  medullary  tube  separates  from  the  epi- 
dermal ectoderm,  some  cells  become  detached  from  the  medial  dorsal 
portion  of  the  tube  and  pass  down  on  either  side  of  it,  as  shown  in  Fig.  125, 
C  and  D.  These  cells  constitute  the  neural  crest.  They  multiply  by 
mitosis  and  accumulate  in  paired  masses,  corresponding  in  number  with 


134 


HISTOLOGY 


the  segments  of  the  body.  Thus  they  form  the  spinal  ganglia.  A  typical 
cell  of  a  spinal  ganglion  is  at  first  round,  but  later  becomes  bipolar  by  send- 
ing out  two  processes,  one  toward  the  periphery  and  the  other  toward'  the 
medullary  tube.  These  processes  grow  out  from  opposite  ends  of  the  cell 
(Fig.  126).  With  further  growth  the  nucleated  cell  body  passes  to  one 
side  of  the  prolongations,  with  which  it  remains  connected  by  a  slender 
stalk.  Such  T-shaped  cells  are  characteristic  of  the  spinal  ganglia.  The 
fibers  which  grow  toward  the  medullary  tube  enter  its  outer  part  and  then 
bifurcate,  sending  one  branch  toward  the  brain  and  the  other  down  the 
cord.  These  longitudinal  fibers  form  distinct  oval  bundles  just  within 
™  „  the  cord,  one  on  either  side  (Fig.  12^,  E). 

Bipolar  cells.  T-cell.     (  •>-> ' 

'Since  these  bundles  receive  accessions  of 
fibers  from  every  spinal  ganglion,  they  en- 
large as  they  approach  the  brain.  The 
fibers  of  the  oval  bundle  branch  freely  at 
their  terminations,  and  along  their  course 
they  give  off  collateral  branches,  which  enter 

FIG.  126.— SPINAL  GANGLION  CELLS.  .     •  •  :'•'.  U»  •    , 

The]  bipolar  forms  are  from  a  chick  the  deep  substance  of  the  cord.  The  periph- 
eral fibers  from  the  spinal  ganglia  grow  out- 
ward through  the  mesenchyma,  and  terminate  in  sense  organs  or  sen- 
sory endings,  which  will  be  described  presently.  The  fibers  of  the  spinal 
ganglia  are  essentially  sensory  or  afferent,  conveying  impulses  from  the 
periphery  toward  the  cord,  and  up  the  cord  toward  the  higher  nervous 
centers. 

The  efferent  or  motor  fibers  arise  chiefly  from  cells,  the  bodies  of  which 
remain  within  the  central^  nervous  system.  Each  of  these  nerve-forming 
cells,  or  neuroblasts,  sends  out  one  long  process  called  a  neuraxon  (or  axone). 
The  neuraxons  of  the  motor  cells  leave  the  spinal  cord,  near  its  ventral 
surface,  in  bundles  which  unite  to  form  the  ventral  roots.  The  ventral 
roots  correspond  in  number  with  the  dorsal  roots,  which  are  the  bundles 
of  sensory  fibers  passing  into  the  cord  from  each  spinal  ganglion.  Periph- 
erally the  ventral  root  joins  the  bundle  of  fibers  growing  outward  from 
the  spinal  ganglion,  and  the  two  together  form  a  spinal  nerve.  Every 
spinal  nerve  consequently  has  a  dorsal  (sensory)  root,  and  a  ventral 
(motor)  root.  The  fibers  from  the  two  roots  travel  in  the  same  connective 
tissue  sheath,  but  otherwise  they  remain  entirely  distinct. 

The  fundamental  facts  which  have  just  been  reviewed  eluded  anatomists  for 
centuries.  The  nerves,  extending  from  the  brain  and  cord  to  all  the  important  organs, 
were  regarded  as  tubes,  conveying  a  vital  fluid  necessary  for  organic  activity;  when 
this  supply  was  cut  off,  the  organs  ceased  to  perform  their  functions.  Thus  if  nerves 
to  the  skin  were  destroyed,  the  skin  became  insensible;  or  if  those  to  muscles  were 
cut,  the  muscles  could  not  contract.  The  possible  existence  of  sensory  and  motor 
nerves  with  different  functions  was  debated  and  generally  rejected,  until  Charles  Bell 
proved  conc'nsively  that  "nerves  entirely  different  in  function  extend  through  the 


NERVOUS    TISSUE 


135 


frame;  those  of  sensation;  those  of  voluntary  motion;  ....  these  nerves  are  some- 
times separate,  sometimes  bound  together;  but  they  do  not,. in  any  case,  interfere  with 
or  partake  of  each  other's  influence."  This  brilliant  discovery  was  verified  by  physio- 
logical experiments  to  determine  "whether  the  phenomena  exhibited  on  injuring 
the  separate  roots  of  the  spinal  nerves  corresponded  with  what  was  suggested  by  their 
anatomy."  Bell  found  that  such  was  the  fact.  (An  Exposition  of  the  Natural 
System  of  the  Nerves  of  the  Human  Body,  with  a  republication  of  papers  delivered 
to  the  Royal  Society,  London,  1824.) 

It  was  at  first  supposed  that  the  nerves  grew  out  from  the  cord  and  brain  and 
acquired  connections  with  their  end-organs;  but  the  apparent  difficulty  which  the 
fibers  would  have  in  reaching  them,  and  the  fact  that  the  connections  must  be  es- 
tablished before  the  nervous  system  can  be  functional,  have  led  to  the  idea  that  the 
nervous  and  muscular  systems  are  connected  at  all  stages  of  their  development.  In 
tadpoles,  however,  Harrison  has  shown  that  such  connection  is  not  an  indispensable 
requisite  for  the  normal  development  of  the  muscles,  since  they  are  formed  in  a  normal 
manner  after  the  medullary  tube  and  neural  crest  have  been  removed  from  the  entire 
posterior  portion  of  the  body.  He  finds  further  that  nerves  grow  out  into  the  adjacent 


A  B 

F;G.  127. — THE  GROWTH  OF  NERVES  IN  TISSUE  CULTURES.    (Harrison.) 

A,  Two  views  of  the  same_  nerve  fiber  taken  twenty-five  minutes  apart,  during  which  time  the  fiber  has 
grown  20//;  B,  Two  views  of  another  fiber,  at  lower  magnification,  taken  fifty  minutes  apart. 


tissues  from  transplanted  portions  of  the  medullary  tube.  Therefore  he  concludes 
that  the  nerves  normally  grow  out  to  their  end-organs  and  unite  with  them,  but  that 
this  takes  place  very  early  in  development,  when  the  paths  are  quite  direct.  Subse- 
quent growth  of  the  body  causes  the  muscles  to  shift  about  and  become  widely  sepa- 
rated from  the  central  nervous  system,  so  that  the  nerves  become  greatly  elongated 
and  follow  irregular  courses  (Amer.  Journ.  Anat.,  1904,  vol.  3,  pp.  197-220;  1906, 
vol.  5,  pp.  121-131). 

The  participation  of  the  mesoderm  in  the  formation  of  nerve  fibers  has  repeatedly 
been  asserted,  and  some  authorities  now  consider  that  the  long  fibers  passing  from  the 
spinal  cord  to  distant  muscles  are  formed  from  chains  of  cells,  either  mesodermal 
or  ectodermal.  Certain  of  Harrison's  experiments  were  designed  to  show  whether 
the  nerve  fibers  are  formed  by  peripheral  cells  or  grow  out  from  the  central  nervous 
system.  In  tissue  cultures,  made  by  placing  fragments  of  the  medullary  tube  of  tad- 
poles in  lymph,  at  a  stage  when  the  tube  consists  entirely  of  round  cells,  he  observed 
the  actual  growth  of  the  fibers.  Examined  after  a  day  or  two  of  cultivation,  in  a 
considerable  number  of  cases,  they  were  seen  extending  out  into  the  lymph  clot  (Fig. 
127).  Harrison  concludes  that  the  nerve  fibers  begin  as  an  outflow  of  J^yaline  pro  to- 


136 


HISTOLOGY 


plasm  from  the  nerve  cells.  The  protoplasm  is  actively  amoeboid,  and,  as  a  result  of 
this  activity,  it  extends  farther  and  farther  from  its  cells  of  origin,  retaining  its  pseudo- 
podia  at  its  distal  end.  Similarly  enlarged  "cones  of  growth,"  provided  with  spiny 
processes,  have  been  observed  in  preserved  tissue  by  Cajal;  and  His,  from  embryo- 
logical  studies,  had  long  maintained  that  the  nerve  fibers  grow  out  from  neuroblasts 
in  the  central  nervous  system  and  spinal  ganglia.  Harrison  concludes  that  his  experi- 
ments "place  the  outgrowth  theory  of  His  upon  the  firmest  possible  basis"  (Anat. 
Rec.,  1908,  vol.  2,  pp.  385-410). 

Dorsal  and  Ventral  Rami.     Every  spinal  nerve,  near  the  junction  of 
its  ganglionic  and  motor  roots,  divides  into  a  dorsal  and. a  ventral  branch 


FIG.  128. — THE  SYMPATHETIC  SYSTEM  IN  A  i6-MM.  HUMAN  EMBRYO.  (After  Streeter.) 
The  ganglionated  trunk  is  heavily  shaded.  The  first  and  last  cervical,  thoracic,  lumbar,  sacral  and  coccygeal 
spinal  ganglia  are  numbered,  a,  Aorta;  ace,  accessory  nerve;  car,  carotid  artery;  cil,  ciliary  ganglion; 
coe,  cceliac  artery;  Ht,  heart;  nod,  nodose  ganglion;  ot,  otic  ganglion;  pet,  petrosal  ganglion;  s-m,  sub- 
maxillary  ganglion;  s.  mes.,  superior  mesenteric  artery;  sph-p.,  sphenopalatine  ganglion;  spl,  splanchnic 
nerve;  St.,  stomach. 

or  ramus  (Fig.  125,  E).  Each  ramus  receives  both  sensory  and  motor 
fibers,  and  is  therefore  a  mixed  nerve.  The  dorsal  rami  are  distributed  to 
the  muscles  and  skin  of  the  back;  their  terminal  cutaneous  branches  enter 
the  skin  along  a  line  extending  from  the  neck  down  the  trunk  of  the  body, 


NERVOUS   TISSUE  137 

as  may  readily  be  shown  in  dissections  of  the  adult.  In  embryos  of  10-12 
mm.  these  rami  are  present  as  short  branches,  which  can  be  followed  to  the 
muscular  condensations  derived  from  the  myotomes,  but  apparently  at 
that  stage  they  do  not  enter  the  skin.  The  ventral  rami  are  longer.  Most 
of  them  anastomose  with  the  ventral  rami  of  adjacent  nerves,  thus  giving 
rise  to  the  cervical,  brachial  and  lumbo-sacral  plexuses.  They  are  dis- 
tributed to  the  muscles  and  skin  of  the  ventral  body  wall. 


DEVELOPMENT  OF  THE  SPINAL  SYMPATHETIC  SYSTEM. 

In  mammalian  embryos  measuring  10-12  mm.,  each  of  the  thoracic 
spinal  nerves  exhibits  a  branch  directed  toward  the  aorta,  and  ending  in  a 
rounded  mass  of  ganglion  cells.  This  is  the  sympathetic  or  visceral  ramus, 
terminating  in  a  sympathetic  ganglion  (Fig.  125,  E).  It  is  generally 
believed  that  the  cells  in  the  sympathetic  ganglia  migrate  outward  from 
those  in  the  spinal  ganglia,  but  an  origin  from  cells  of  the  medullary  tube 
which  wander  out  along  the  ventral  roots  has  also  been  asserted.  Al- 
though the  cells  of  the  sympathetic  ganglia  were  formerly  considered  to  be 
mesodermal  (even  after  it  had  been  shown  that  those  of  the  spinal  ganglia 
were  ectodermal),  it  is  now  generally  admitted  that  the  entire  sympathetic 
system  is  ectodermal.  However,  in  the  cervical  region  the  spinal  nerves 
at  first  do  not  have  sympathetic  rami,  and  the  sympathetic  ganglia  con- 
sequently appear  isolated  in  the  mesenchyma.  Their  cells  may  have  mi- 
grated in  detached  groups.  Instead  of  eight  ganglia  on  either  side  of  the 
neck,  corresponding  in  number  with  the  spinal  nerves,  there  are  but  three, 
known  as  the  superior,  middle  and  inferior  cervical  ganglia,  respectively, 
and  of  these  the  middle  ganglion  may  be  merged  with  the  superior.  They 
are  elongated  structures,  especially  the  superior  ganglion,  and  presumably 
represent  a  fusion  of  segmental  ganglia. 

Each  sympathetic  ganglion  in  the  thorax  of  the  adult  is  connected 
with  its  spinal  nerve  by  two  rami  communicantes,  known  as  the  white  and 
gray  rami,  respectively.  The  white  rami  consist  chiefly  of  fibers  passing 
outward  from  the  spinal  nerve,  and  they  are  probably  a  persistence  of  the 
sympathetic  rami  of  the  embryo.  The  gray  rami  contain  fibers  passing 
from  the  sympathetic  ganglia  back  to  the  spinal  nerves,  and  apparently 
arise  later.  They  are  found  not  only  in  the  thorax  and  abdomen,  but 
also  in  the  neck  where,  as  usually  described,  they  place  the  superior  cervi- 
cal ganglion  in  connection  with  the  first  four  cervical  nerves,  the  middle 
cervical  ganglion  in  connection  with  the  fifth  and  sixth,  and  the  inferior 
in  connection  with  the  sixth,  seventh  and  eighth.  The  succession  of 
sympathetic  ganglia  on  either  side  of  the  body,  extending  from  the  neck 
to  the  pelvis,  become  connected  with  one  another  through  bundles  of 


138  HISTOLOGY 

longitudinal  nerve  fibers,  and  thus  they  form  the  ganglionated  trunk  oj 
the  sympathetic  nerve  (Fig.  128). 

From  the  ganglia  of  the  trunk,  bundles  of  nerve  fibers  grow  out  ven- 
trally  to  supply  the  blood  vessels  and  viscera.  It  is  characteristic  of  these 
branches  that  they  unite  with  one  another  freely,  forming  net-like  sym- 
pathetic plexuses,  within  which  there  are  many  scattered  nerve  cells. 
When  the  nerve  cells  in  these  ganglionated  plexuses  are  particularly  abun- 
dant, the  structure  is  called  a  ganglion,  though  generally  retaining  a 
plexiform  character. 

The  principal  branches  of  the  cervical  sympathetic  trunk  are  the  su- 
perior, middle,  and  inferior  cardiac  nerves,  which  grow  out  from  the  corre- 
sponding cervical  ganglia.  They  extend  to  the  heart  (Fig.  128)  and  form 
the  cardiac  plexus,  associated  with  which  is  the  cardiac  ganglion,  situated 
under  the  arch  of  the  aorta.  These  nerves,  which  are  joined  by  branches 
from  the  vagus,  innervate  the  heart.  The  cervical  sympathetic  trunks 
also  send  out  nerves  which  form  plexuses  around  the  aorta  and  the  pul- 
monary, subclavian  and  carotid  arteries  to- 
gether with  their  branches.  These  innervate 
the  smooth  muscles  in  the  walls  of  the  vessels. 
Some  of  the  fibers  accompany  the  thyreoid 
arteries  into  the  thyreoid  gland  and  others  are 
distributed  to  the  pharynx  and  larynx. 

The  upper  thoracic  ganglia  supply  nerves 
to  the  aortic  plexus  and  pulmonary  plexus,  and 
the  latter  enters  the  lungs.     Large  bundles  of 
fibers  proceeding  from  the  "  fifth  or  sixth  to  the 
ninth  or  tenth"  thoracic  ganglia  of  the  sympa- 
thetic  trunk,  unite  to  form  the  greater  splanchnic 
nerves>   one   on  either  side  of  the  body,  and 
wphitrs        branches  from  the  remaining  thoracic  ganglia 
form    the    lesser    splanchnic    nerves.       These 
myentefi?p?exus° lbna.; pL^su?-   splanchnic  nerves  pass  into  the  abdominal  cavity 

mucous  plexus.  .    .    .  .  .  .  .. 

and  join  one  another,  forming  a  large  ganglion- 
ated plexus  on  the  sides  and  front  of  the  aorta  (Fig.  128).  The  sympa- 
thetic trunks  in  the  abdomen  also  send  branches  to  join  this  plexus.  The 
great  plexiform  ganglion  found  around  the  cceliac  artery,  as  it  leaves 
the  aorta,  is  called  the  cceliac  ganglion  (or  plexus).  A  similar  plexus 
surrounds  the  superior  mesenteric  artery.  From  these  plexuses,  as  shown 
in  the  diagram  (Fig.  129),  sympathetic  nerves  extend  through  the  mesen- 
tery, and  they  form  a  microscopic  ganglionated  plexus  surrounding  the 
intestinal  tube,  lodged  between  the  longitudinal  and  circular  layers  of 
smooth  muscle.  This  is  the  myenteric  plexus  (plexus  my  enter  icus) .  It 
innervates  the  muscle  and  sends  branches  into  the  tissue  beneath  the  mu- 


NERVOUS    TISSUE  139 

cous  membrane,  where  they  form  another  plexus  (the  plexus  submu- 
cosus).  In  this  way  the  sympathetic  system  supplies  the  intestine. 
It  sends  its  fibers  into  other  organs,  following  the  arteries,  thus  forming 
the  hepatic,  splenic,  suprarenal  and  renal  plexuses.  In  the  pelvis  the 
sympathetic  rami  form  the  hypogastric  pi  exus,  with  branches  distributed 
to  the  rectum,  bladder  and  urogenital  organs,  and  finally  it  accompanies 
the  arteries  down  the  legs,  innervating  the  muscles  in  the  walls  of  the 
vessels. 

In  1664,  Willis  published  a  remarkably  clear  account  of  the  nerve  "commonly 
called  intercostal  because  it  rests  against  the  roots  of  the  ribs."  This  nerve,  which  is 
the  ganglionated  trunk  of  the  sympathetic  system,  had  generally  been  supposed  to 
descend  from  the  cerebral  nerves.  Willis  described  its  connections  with  these  nerves 
and,  through  each  intercostal  space,  with  the  spinal  cord.  He  noted  the  cardiac 
branches,  and  stated  that  the  great  mesenteric  plexus,  placed  in  the  midst  of  the  others, 
like  a  sun,  sent  its  nerve  fibers  like  rays  in  all  directions  (hence  it  came  to  be  called  the 
"solar  plexus").  Willis  found  that  this  nerve  sent  branches  to  all  the  abdominal 
organs  below  the  stomach.  He  considered  that  its  function  was  to  place  the  heart 
and  viscera  in  connection  with  the  brain  so  that  they  should  act  in  harmony 
(Anatome  cerebri,  Amstelodami,  1664).  Because  of  their  frequent  communications 
with  other  nerves,  Winslow  (1732)  called  the  ganglionated  trunks  the  Nervi  sympa- 
thetici  maximi. 

Bichat  (Anatomic  Generale,  1802,  translated  by  Hayward  1822)  subdivided  the 
nervous  system  into  two  parts  "essentially  distinct  from  each  other,  the  one  having 
the  brain  and  its  dependencies  for  its  principal  center,  and  the  other  having  the  gang- 
lions." The  latter  is  "almost  everywhere  distributed  to  the  organs  of  digestion, 
circulation,  respiration,  and  secretion."  "Each  ganglion  is  a  distinct  center,  inde- 
pendent of  the  others  in  its  action,  furnishing  or  receiving  particular  nerves  as  the 
brain  furnishes  or  receives  its  own.  .  .  .  The  continuous  thread  that  is  observed 

from  the  neck  to  the  pelvis  is  nothing  but  a  series  of  communications These 

communications  are  often  interrupted,  without  any  inconvenience  in  the  organs  to 
which  the  great  sympathetic  goes."  That  the  sympathetic  system  acts  independently 
of  the  central  nervous  system,  at  least  to  a  great  extent,  is  its  most  prominent  physio- 
logical characteristic. 

Thus  the  sympathetic  system  merits  to  some  extent  the  terms  organic,  visceral, 
or  vegetative  system,  which  have  been  applied  to  it.  Burdach  (1819)  stated  that  it 
might  be  called  the  "automatic  system,"  and  the  term  "autonomic  system"  has  more 
recently  been  used,  but  Burdach  preferred  sympathetic  system,  which  has  been  inter- 
nationally adopted  by  anatomists. 


DEVELOPMENT  OF  THE  CEREBRAL  NERVES. 

The  nerves  which  are  connected  with  the  brain,  supplying  the  skin  and 
muscles  of  the  head  together  with  certain  viscera,  are  built  upon  the 
same  plan  as  the  spinal  nerves,  of  which  they  may  be  regarded  as  a  continu- 
ation. They  consist  of  dorsal  sensory  roots,  and  ventral  motor  roots 
which,  however,  do  not  unite  to  form  single  nerves.  Certain  cerebral 
nerves  are  wholly  sensory  and  others  consist  merely  of  a  ventral  root,  and 


140 


HISTOLOGY 


are  therefore  entirely  motor.  Still  others  have  no  ventral  roots,  but  re- 
ceive motor  fibers  through  lateral  roots.  The  fibers  in  the  lateral  roots  are 
like  motor  fibers  of  the  ventral  roots  in  that  they  arise  from  cells  within 
the  central  nervous  system,  but  their  processes  emerge  from  the  lateral 
wall  of  the  brain  instead  of  the  ventral  wall.  They  come  out  immediately 
below  the  entering  sensory  fibers  of  the  dorsal  roots. 

Beginning. at  the  anterior  end  of  the  brain  and  proceeding  toward 
the  spinal  cord,  the  cerebral  nerves  occur  in  the  following  order:  olfactory, 
optic,  oculomotor,  trochlear,  trigeminal,  abducent,  facial,  acoustic,  glosso- 
pharyngeal,  vagus,  accessory  and  hypoglossal. 


FIG.  130. — THE  CEREBRAL  NERVES  OF  A  I2-MM.  PIG. 

Olfactory  (not  shown).  Optic  (fibers  in  the  stalk  of  the  eye,  the  lens  of  which  is  marked  L).  Oculomotor 
(Oc.).  Trochlear  (Tr.).  Trigeminal, — semilunar  ganglion  (s.-l.);  ophthalmic  (oph.),  maxillary 
(mx.)  and  mandibular  (md.)  branches.  Abducent  (Ab.).  Facial, — geniculate  ganglion  (g.);  large 
superficial  petrosal  (1.  s.  p.),  chorda  tympani  (ch.  ty.),  and  facial  (fa.)  branches.  Acoustic  (A.),  supply- 
ing the  otocyst  (Ot.).  Glossopharyngeal, — superior  (s.)  and  petrosal  (p.)  ganglia;  tympanic  (t.)t  lingual 
(1.  r.)  and  pharyngeal  (ph.  r.)  branches.  Vagus, — jugular  (j.)  and  nodose  (n.)  ganglia;  auric- 
ular (au.)  and  laryngeal  branches,  rec.  being  the  recurrent  nerve;  the  main  stem  proceeds  to  the  abdo- 
men. Accessory, — internal  ramus  joining  the  vagus,  and  external  ramus  (ex.).  Hypoglossal  (Hy.). 
Froriep's  rudimentary  hypoglossal  ganglion  (F.)  sometimes  sends  fibers  to  the  hypoglossal  nerve,  c.1, 
c.2,  c.3,  cervical  nerves. 

It  is  desirable  to  use  the  names  of  these  nerves  rather  than  the  numbers 
often  applied  to  them.  The  names  are  descriptive,  but  the  numbers  are 
arbitrary  and  were  very  variously  employed  in  the  older  anatomical  works. 
Unlike  the  spinal  nerves,  the  cerebral  nerves  are  not  a  series  of  similar 
structures.  Moreover  the  recent  demonstration  of  the  Nervus  terminalis 
in  mammals  indicates  that  the  numbering  may  need  further  revision. 

In  embryos  measuring  about  10  mm.,  the  cerebral  nerves  are  all  present 
and  show  their  primary  branches.  Except  the  olfactory  nerve,  they  are 


NERVOUS   TISSUE  141 

included  in  Fig.  130,  in  which  parts  derived  from  dorsal  roots  are  unshaded; 
those  from  lateral  roots  are  black;  and  those  from  ventral  roots  are  cross- 
hatched.  They  may  be  briefly  described  as  follows. 

The  olfactory  nerve,  on  either  side  of  the  head,  consists  of  about  twenty  separate 
bundles  of  processes  from  the  neuro-epithelial  cells  in  the  nasal  mucous  membrane. 
These  bundles  of  neuro-epithelial  fibers  pass  directly  into  the  olfactory  bulbs,  which  are 
portions  of  the  brain.  The  wmero-nasal  nerve  is  a  bundle  much  longer  than  the  others, 
which  arises  from  a  tubular  epithelial  pocket^in  the  mucous  membrane  of  the  nasal  sep- 
tum. This  pocket  is  a  rudimentary  organ  of  considerable  interest,  known  as  the  vomero- 
nasal  (or  Jacobson's)  organ.  Associated  with  the  vomero-nasal  nerve,  but  said  to  be 
distinct  from  it,  there  is  a  small  ganglionated  nerve  which  sends  its  fibers  into  the 
brain  caudal  to  the  olfactory  lobe.  Distally  it  is  "  distributed  chiefly  to  the  vomero- 
nasal  organ."  This  is  the  Nervus  terminate,  discovered  in  fishes  by  Pinkus  in  1894, 
and  recently  found  in  human  and  pig  embryos  and  in  adult  dogs  and  cats  (Johnston, 
Journ.  Comp.  Neur.,  1913,  vol.  23,  pp.  97-120;  and  McCotter,  ibid.,  pp.  145-152). 

The  optic  nerve  is  a  round  cord  of  fibers  extending  from  ganglion  cells  in  the  retina 
to  the  brain.  It  is  quite  unlike  any  portion  of  a  spinal  nerve,  and  will  be  described 
in  connection  with  the  eye. 

The  oculomotor  nerve  has  only  a  ventral  root,  and  consequently  it  is  entirely  motor. 
It  is  distributed  to  four  of  the  six  muscles  which  move  the  eye-ball  (namely,  the  inferior 
oblique  and  the  superior,  medial  and  inferior  rectus  muscles)  and  to.  the  muscle  which 
raises  the  upper  eye-lid  (M.  levator  palpebrce  superioris] . 

The  trochlear  nerve  arises  from  cells  in  the  ventral  part  of  the  medullary  tube,  but 
its  fibers,  instead  of  passing  directly  outward,  grow  to  the  dorsal  surface  of  the  tube  and 
cross  to  the  opposite  side  before  they  emerge.  Although  the  trochlear  nerve  must 
be  regarded  as  a  ventral  root,  its  fibers  leave  the  brain  more  dorsally  than  those  of 
any  other  nerve.  They  come  out  at  the  notch  or  isthmus  between  the  mid-brain  and 
the  hind-brain,  and  all  of  them  pass  to  the  superior  oblique  muscle  of  the  eye-ball. 
This  muscle,  which  runs  through  a  fibrous  ring  or  pulley  (trochled)  attached  to  the 
frontal  bone,  turns  the  eye  outward  and  downward. 

The  trigeminal  nerve  consists  of  dorsal  and  lateral  roots.  Its  sensory  cells  form  the 
semilunar  ganglion,  which  gives  rise  to  three  large  nerves,  the  ophthalmic,  maxillary 
and  mandibular  (hence  the  name  trigeminal}.  In  general  terms,  "the  ophthalmic  is 
the  sensory  nerve  of  the  forehead  and  largely  of  the  scalp;  the  maxillary  is  the  sensory 
nerve  of  the  front  of  the  face  and  the  upper  teeth;  and  the  mandibular  distributes 
sensory  fibers  to  the  front  of  the  tongue,  the  lower  teeth,  and  the  skin  over  the  lower 
jaw.  Unlike  the  ophthalmic  and  maxillary  nerves,  the  mandibular  is  a  mixed  nerve, 
receiving  all  the  motor  fibers  of  the  trigeminal.  These  motor  fibers  are  distributed 
chiefly  to  the  muscles  of  mastication,  through  the  masticator  nerve. 

The  abducent  nerve  is  wholly  a  ventral  root,  and  its  fibers  all  pass  to  the  lateral  rec- 
tus muscle,  which  abducts  the  eye-ball  (i.e.,  turns  it  outward). 

The  facial  nerve  is  largely  a  lateral  root,  and  is  the  motor  nerve  of  the  facial  muscles. 
It  has,  however,  a  dorsal  root  (the  so-called  Nervus  intermedius)  and  a  ganglion 
known  as  the  ganglion  geniculi,  or  geniculate  ganglion,  since  it  occurs  at  a  bend  in 
the  nerve.  The  facial  nerve  has  three  fundamental  branches,  all  of  which  contain 
both  sensory  and  motor  fibers;  these  are  the  large  superficial  petrosal  nerve,  the  chorda 
tympani,  and  the  facial  nerve  (the  name  of  the  entire  nerve  being  applied  to  one  of 
its  parts). 

The  acoustic  nerve,  which  is  wholly  associated  with  the  internal  ear,  is  entirely  sen- 


142  HISTOLOGY 

sory.  Its  large  ganglion  becomes  subdivided  into  the  vestibular  ganglion,  with  fibers 
to  the  semicircular  ducts  or  "organ  of  equilibration,"  and  the  spiral  ganglion,  which 
sends  fibers  to  the  auditory  cells  of  the  cochlea. 

The  glosso-pharyngeal  nerve  is  chiefly  sensory,  but  it  has  a  small  lateral  motor 
root.  It  has  two  ganglia,  one  above  the  other,  the  superior  ganglion  (ganglion  superius] 
and  the  petrosal  ganglion  (ganglion  petrosum),  respectively.  The  principal  branches 
are  the  sensory  tympanic  nerve,  which  supplies  the  mucous  membrane  of  the  middle 
ear;  the  sensory  lingual  branch,  which  passes  to  the  back  of  the  tongue  and  ends  in 
contact  with  cells  of  the  taste  buds,  being  the  nerve  of  taste;  and  the  mixed  pharyngeal 
branch  which  is  distributed  to  the  pharynx.  It  supplies  the  stylo-pharyngeal  muscle. 

The  vagus  nerve,  which  is  sensory,  is  joined  by  the  accessory  nerve,  which  is  motor, 
so  that  the  vagus  is  regarded  as  a  mixed  nerve.  It  has  two  ganglia,  the  jugular  ganglion 
(ganglion  jugulare)  above,  and  the  nodose  ganglion  (ganglion  nodosum)  below. 
Its  principal  branches  are  the  sensory  auricular  branch,  which  is  distributed  to  the 
skin  of  the  external  ear;  the  mixed  superior  laryngeal  nerve,  distributed  to  certain 
laryngeal  muscles  and  to  the  mucous  membrane  of  the  larynx  down  to  the  vocal 
folds;  the  recurrent  nerve,  which  terminates  as  the  superior  laryngeal  in  the  vocal 
muscles  and  mucous  membrane  of  the  lower  part  of  the  larynx;  cardiac  branches, 
which  anastomose  with  the  cardiac  sympathetic  plexus;  and  finally,  from  the  main 
trunk  of  the  nerve  as  it  passes  through  the  thorax  into  the  abdomen,  branches  to 
the  oesophagus,  trachea,  lungs,  stomach,  small  intestine,  liver,  spleen  and  kidneys. 
Many  of  these  branches  anastomose  with  the  sympathetic  system.  The  wide 
range  of  this  nerve  is  indicated  by  the  term  vagus. 

The  accessory  nerve  is  wyholly  motor,  and  consists  of  lateral  roots  which  arise  from 
the  hind-brain,  and  also  from  the  spinal  cord  as  far  down  as  the  sixth  cervical  ganglion. 
Beginning  as  a  small  bundle  of  fibers  underneath  the  dorsal  roots  on  the  side  of  the 
spinal  cord,  it  increases  in  size  as  it  passes  upward  toward  the  brain,  receiving  acces- 
sions of  fibers  in  its  course.  It  arches  toward  the  vagus  and  descends  in  contact 
with  it,  finally  dividing  into  external  and  internal  branches.  The  external  ramus 
supplies  the  sterno-mastoid  muscle  and  a  part  of  the  trapezius;  the  internal  ramus 
joins  the  vagus. 

The  hypoglossal  nerve  is  made  up  entirely  of  ventral  roots,  and  is  the  motor  nerve 
for  the  lingual  muscles. 

In  the  head  the  sympathetic  system  is  intimately  associated  with  the. 
cerebral  nerves,  along  the  main  branches  of  which  the  ganglion  cells  mi- 
grate. They  accumulate  in  four  ganglia,  all  of  which  are  associated  with 
the  trigeminal  nerve.  These  are  the  ciliary,  spheno-palatme,  otic  and 
submaxillary  ganglia  (Fig.  128). 

The  'ciliary  ganglion  receives  its  cells  from  the  ophthalmic  nerve  and  in  part  from 
the  oculomotor  nerve,  with  both  of  which  it  remains  permanently  connected.  The 
sympathetic  plexus  which  ascends  around  the  internal  carotid  artery  also  sends  fibers 
to  it.  Branches  from  the  ciliary  ganglion  are  distributed  to  the  front  of  the  eye, 
especially  to  the  ciliary  muscles  and  the  dilator  of  the  iris. 

The  spheno-palatine  ganglion  derives  most  of  its  cells  from  the  maxillary  nerve,  but 
it  is  in  communication  also  with  the  large  superficial  petrosal  nerve  and  the  sympa- 
thetic plexus  around  the  internal  carotid  artery.  Some  of  its  fibers  reach  the  orbit,  but 
most  of  them  are  distributed  to  the  mucous  membrane  of  the  nose  and  palate. 

The  otic  and  submaxillary  ganglia  both  receive  cells  from  the  mandibular  nerve, 


NERVOUS   TISSUE  143 

and  both  are  in  connection  with  the  sympathetic  plexus  around  neighboring  arteries. 
The  otic  ganglion  receives  fibers  from  a  prolongation  of  the  tympanic  nerve,  and  it 
sends  branches  to  the  parotid  gland.  The  submaxillary  ganglion  is  joined  by  the 
chorda  tympani  and  sends  branches  to  the  submaxillary  and  sublingual  glands. 

The  lower  ganglia  of  the  glossopharyngeal  and  vagus  nerves — the 
petrosal  and  nodose  ganglia — differ  from  the  other  ganglia  in  the  head  by 
being  temporarily  connected  with  rudimentary  ectodermal  sense  organs. 
Their  contact  with  the  ectoderm  is  transient,  however,  and  their  cells 
are  considered  to  have  come  down  from  the  superior  and  jugular  ganglia, 
respectively.  They  are  thus  strikingly  analogous  to  the  ganglia  of  the 
sympathetic  trunk,  and  it  may  be  considered  that  instead  of  being  con- 
nected with  their  nerves  by  rami,  they  have  remained  in  the  main  stems. 
Moreover  the  vagus  nerves  produce  myenteric  and  submucous  plexuses 
in  the  oesophagus  and  stomach,  which  are  quite  like  those  of  the  sympa- 
thetic system  in  the  intestine,  but  the  fibers  pass  from  the  nodose  ganglion 
to  these  plexuses  without  the  interposition  of  a  ganglion  comparable  with 
the  cceliac  ganglion.  In  addition  to  sympathetic  fibers,  the  vagus  con- 
tains many  direct  fibers,  which  probably  come  especially  from  the  jugular 
ganglion.  At  present,  however,  both  the  upper  and  lower  ganglia  are 
described  as  similar  in  structure  and  as  resembling  the  spinal  ganglia. 
The  opinion  here  advanced,  that  the  nodose  and  petrosal  ganglia  are 
sympathetic,  must  therefore  be  regarded  as  tentative. 

STRUCTURE  OF  NERVOUS  TISSUE. 

Owing  to  the  extent  of  the  ramifying  processes  characteristic  of  nerve 
cells,  it  is  rare  that  an  entire  cell,  even  a  small  one,  is  included  within  a 
single  section.  A  motor  cell,  such  as  sends  its  fibers  from  the  cord  to 
distant  muscles,  has  never  been  seen  as  a  complete,  isolated  structure. 
From  what  is  known  of  its  several  parts,  however,  a  diagram  of  such  a 
cell  may  be  put  together,  as  shown  in  Fig.  131.  At  the  top  of  the  figure 
is  the  nucleated  cell  body,  which  in  different  nerve  cells  varies  in  diameter 
from  4-150  ju.  Frequently  this  nucleated  portion  is  referred  to  as  the  nerve 
cell  in  distinction  from  the  processes  which  grow  out  from  it.  The  proc- 
esses include  the  relatively  short  and  irregularly  ramifying  dendrites, 
which  convey  impulses  toward  the  cell  body,  and  a  single  fiber,  the 
neuraxon,  chemically  and  physically  different  from  the  others,  which 
conveys  impulses  away  from  the  cell  body.  If  the  various  processes  radiate 
from  the  cell  body  in  several  directions,  as  in  Fig.  131,  the  cell  is  described 
as  multipolar;  if  the  neuraxon  is  at  one  end  of  the  cell  and  a  single  dendrite 
at  the  other,  the  cell  is  bipolar  (Fig;  126);  sometimes  the  nerve  cell  has 
only  one  process  and  is  unipolar,  as  in  the  mature  cells  of  the  spinal  gang- 
lion which  have  a  T-shaped  process,  and  in  other  cells  in  which  dendrites 


144 


HISTOLOGY 


D.endrites.* 


Cell  body. 


Collaterals. 


Medullary  sheath. 


•  Neurolemma. 


have  not  developed.     The  dendrites  have  the  granular  structure  of  the 
protoplasm  from  which  they  grow  out,  and  were  therefore  originally 

named  "protoplasmic  processes."  The  neur- 
axon, although  receiving  delicate  fibrils  from  the 
protoplasm,  as  shown  by  special  methods,  seems 
quite  distinct  from  the  cell  body.  At  its  origin 
it  often  appears  as  a  clear  slender  cone,  free  from 
granules,  implanted  directly  upon  the  cell  body, 
or  upon  the  root  of  one  of  the  larger  dendrites. 
It  tapers  as.  it  passes  outward,  and  its  fibrils 
come  close  together  so  that  they  appear  to  unite. 
Beyond  the  apex  of  the  cone,  which  is  a  place 
where  the  neuraxon  is  easily  broken,  the  fiber 
enlarges  and  its  constituent  neurofibrils  spread 
apart  so  that  they  are  more  readily  distinguish- 
able. They  are  imbedded  in  a  fluid  interfibrillar 
substance.  The  neuraxon  may  send  out  col- 
lateral branches,  which  are  usually  at  right  angles 
with  the  main  fiber. 

As  the  neuraxon  passes  out  from  a  motor  cell 
it  is  at  first  free  from  any  surrounding  sheath 
(Fig.  131,  a).  In  the  outer  layer  of  the  spinal 
cord  it  becomes  coated  with  a  layer  of  the  re- 
fractive fatty  substance  known  as  myelin.  This 
is  formed  in  the  cord  or  medulla  spinalis,  and 
fibers  which  have  this  sheath  are  said  to  be 
medullated  fibers  (Fig.  131,  b).  The  cells  of  the 
neuroglia  network,  through  which  the  nerve 
passes  while  within  the  cord,  may  take  part  in 
forming  the  myelin,  but  they  do  not  produce  a 
membrane  around  each  nerve,  and  they  are  not 
shown  in  the  diagram.  On  leaving  the  cord,  the 
neuraxon  is  still  surrounded  by  the  myelin  sheath, 
but  the  latter  is  invested  by  a  membrane  called 
the  neurolemma  or  sheath  of  Schwann  (Fig.  131, 
c)*  ^  quite  regular  intervals  along  the  course 
of  tne  fiber,  the  myelin  sheath  is  constricted  or 
interrupted,  forming  the  nodes  of  Ranvier. 
These  are  0.08-1.00  mm.  apart,  being  closer 

.,  .         r-i  j  •      ^.v      j*   ^    i 

together  in  growing  fibers,  and  in  the  distal  part 
of  adult  fibers.  Midway  between  two  nodes 

there  is  a  nucleus,  which  may  be  found  at  any  point  in  the  circumfer- 
ence of   the  fiber,  just  within  the  neurolemma;   it  occupies  a  depres- 


Node  of  Ranvier. 


FIG.  131.  —  DIAGRAM  OF  A  NERVE 

CELL. 


NERVOUS    TISSUE  145 

sion  in  the  myelin.  Toward  its  distal  end  the  fiber  usually  branches, 
and  the  branches  are  given  off  at  the  nodes.  '  The  myelin  then  becomes 
thin,  so  that  the  fiber  is  surrounded  merely  by  neurblemma  (Fig.  131,  d), 
and  finally  this  ends.  The  naked  axis  cylinder  then  breaks  up  in  its 
terminal  arborization,  forming  the  motor  organs  attached  to  striated 
muscle  fibers.  In  comparison  with  the  size  of  its  cell  body,  the  neuraxon 
shown  in  the  diagram  is  too  short;  in  extreme  cases,  as  in  the  neuraxons 
extending  from  the  spinal  cord  to  muscles  in  the  foot,  it  may  be  actually 
more  than  a  meter  long,  or  several  thousand  times  the  diameter  of  the  cell 
body  from  which  it  comes. 

The  medullated  nerve  fibers  were  the  first  parts  of  the  nerve  to  be  studied  micro- 
scopically,, and  were  referred  to  as  " cylinders;"  the  central  fiber  was  called  the  axis 
cylinder.  Remak  (Obs.  anat.  et  micr.  d'e  syst.  nerv.  structura,  Berlin,  1838)  was  the 
first  to  describe  non-medullated  nerves,  which  are  still  known  as  "Remak's  fibers." 
but  their  nervous  nature  was  not  readily  admitted.  Moreover.  Remak  recognized 
that  nerve  fibers  proceed  from  cells.  Deiters  (Untersuchungen  iiber  Gehirn  und 
Riickenmark,  Braunschweig,  1865)  supplemented  these  observations  by  showing 
that  all  "ganglion  cells"  (referring  to  nerve  cells  within  the  spinal  cord  and  brain) 
are  centers  for  two  systems  of  true  nerve  fibers,  (i)  the  generally  broader  and  always 
single  and  undivided  axis  cylinder  process;  and  (2)  the  protoplasmic  processes  with 
their  extensive  system  of  minute  branches.  He  discussed  whether  the  nerve  cells 
anastomose  with  one  another,  and  concluded  that  all  such  anastomoses  which  had 
been  reported  were  due  to  deceptive  appearances.  Thus  the  nerve  cells  were 
believed  to  communicate  by  contact  and  not  by  continuity. 

The  confused  mass  of  interwoven  fibers  which  sections  of  nervous  tissue  ordinarily 
present,  is,  therefore,  not  a  general  syncytium  from  which  sensory  and  motor  fibers  run 
out,  but  an  orderly  arrangement  of  branching  cells.  Striking  proof  of  this  was  afforded 
in  Golgi's  description  of  the  olfactory  bulb  (1875).  In  the  plate  which  accompanied 
his  publication,  the  cells  in  the  different  layers,  and  their  various  processes,  were 
drawn  in  black  with  absolute  assurance;  similar  figures  of  "Golgi  preparations" 
are  now  seen  in  all  treatises  on  the  anatomy  of  the  nervous  system  (Fig.  132).  Golgi 
found  that  if  fresh  tissue  is  placed  in  a  solution  of  potassium  bichromate  and  osmic 
acid,  and  is  later  transferred  to  a  solution  of  silver  nitrate,  a  heavy  black  deposit 
occurs  in  certain  nerve  cells,  extending  throughout  their  minutest  ramifications, 
whereas  adjacent  cells  are  wholly  unaffected.  The  process  must  be  carried  out 
with  great  care,  and  even  then  it  is  capricious;  but  this  method  has  afforded  funda- 
mental information  in  regard  to  the  forms  of  individual  nerve  cells. 

In  order  to  emphasize  that  the  nervous  system  is  built  up  of  separate 
cells,  the  term  neurone  has  been  widely  used  to  designate  a  complete  nerve 
cell,  with  all  its  branches.  Fig.  131,  therefore,  represents  a  neurone,  to- 
gether with  certain  sheath  cells. 

Recently,  however,  there  has  been  a  tendency  to  regard  such  a  neurone  as  a 
syncytium,  and  in  the  latest  editions  of  his  "Lehrbuch,"  Stohr  adopts  this  interpreta- 
tion. He  states  that  in  so  far  as  the  neurone  includes  peripheral  nerve  fibers,  it  is 
a  biological  or  syncytial  unit,  but  not  a  single  cell.  It  is  considered  to  be  a  "biological 
unit"  since  it  is  well  known  that  the  cell  body  of  the  nerve  cell  is  the  nutritive  or 


146 


HISTOLOGY 


controlling  center  for  the  entire  fiber;  and  any  part  of  the  fiber  which  is  cut  off  from 
the  cell  body  undergoes  degeneration.  Stohr  considers  that  Schwann  (1839)  had 
the  correct  conception  when  he  regarded  the  nerve  fiber  as  "  a  secondary  cell,  devel- 
oped by  the  coalescence  of  primary  cells." 

Opposed  to  the  syncytial  interpretation  of  a  peripheral  fiber  are  the  experiments 
of  Harrison,  some  of  wrhich  have  already  been  cited.  He  has  shown  that  in  the 
tadpole  the  sheath  cells,  or  neurolemma  cells,  which  are  believed  by  some  to  produce 
the  segments  of  the  fiber  which  they  surround,  all  migrate  from  the  brain  along  the 
dorsal  root.  If  the  dorsal  part  of  the  cord  is  removed  from  tadpoles,  the  ventral 
roots  are  deprived  of  their  sheath  cells,  but  the  fibers  of  the  ventral  roots  grow  out  to 
their  terminations  nevertheless.  If  the  ventral  part  of  the  cord  is  cut  from  beneath 
the  dorsal  part,  the  dorsal  roots  develop  and  have  with  them  the  sheath  cells  which 


Neuraxpn  with 
branching  col- 
laterals. 


FIG.  132. — Two  NERVE  CELLS  FROM  THE  CENTRAL   NERVOUS  SYSTEM.     GOLGI  PREPARATIONS.     X  200. 

A,  Cell  of  Deiter's  type,  having  a  neuraxon  ending  at  a  considerable  distance  from  the  cell  body;  B,  cell  of 

Golgi's  type  having  a  neuraxon  with  many  branches  ending  near  the  cell  body. 

normally  would  enclose  the  fibers  of  the  ventral  root.  These  sheath  cells  do  not 
produce  nerve  fibers.  Therefore  Harrison  concludes  that  the  peripheral  fibers  are 
not  syncytial. 

Recently  W.  H.  and  M.  R.  Lewis  have  caused  sympathetic  fibers  to  grow  from 
pieces  of  the  intestine  of  chick  embryos  placed  in  various  saline  solutions.  These 
fibers  show  amoeboid  endings.  They  branch  freely  and  anastomose,  but  like 
the  nerve  fibers  from  the  central  nervous  system  "they  are  outgrowths  from  nerve 
cells  and  are  not  formed  from  pre-existing  protoplasmic  networks"  (Anat.  Rec.,  1912, 
vol.  6,  pp.  7-31). 

Another  form  of  syncytium  would  result  if  neurofibrils  passed  across  the  places 
of  contact  between  the  neurones.  According  to  Apathy,  who  has  studied  the  neuro- 
fibrils of  invertebrates  with  special  methods  and  faultless  technique,  the  neurofibrils 
pass  freely  from  cell  to  cell  (Mitth.  Zool.  Station,  Naples,  1897,  vol.  12,  pp.  495-748). 
It  is  possible  that  this  takes  place  in  the  vertebrate  nervous  system  also.  Anastomoses 


NERVOUS    TISSUE 


147 


have  been  found  between  ganglion  cells  in  the  retina  by  Dogiel,  and  slender  nerve 
fibers  appear  to  anastomose  in  tissue  cultures;  but  the  staining  of  individual  cells 
by  the  Golgi  method,  and  the  way  in  which  degeneration  may  be  limited  to  cell 
territories,  are  regarded  as  strong  evidence  against  the  existence  of  a  general  syncytium. 

STRUCTURE  OF  GANGLIA. 

Although  a  ganglion  is  characterized  by  the  accumulation  of  the  bodies 
of  nerve  cells,  it  is  traversed  by  many  fibers,  as  seen  in  the  section  of  a 
spinal  ganglion  (Fig.  133).  Under  higher  magnification  the  cell  bodies 
appear  as  in  Fig.  134.  The  nuclei  are  large  vesicular  structures,  round 
or  oval  in  outline,  containing  a  characteristic  prominent  nucleolus.  They 
are  surrounded  by  abundant,  darkly  staining,  finely  granular  proto- 


Blood  vessel. 


Fat. 


Ganglion  cells. 


Nerve  fibers. 


Perineurium. 


root 
of  a  spinal  nerve. 

Center 

of  the 

spinal 

ganglion. 

FIG.  133. — LONGITUDINAL  SECTION  THROUGH  A  SPINAL  GANGLION  OF  A  CAT.     X  18. 


plasm,  which  exhibits  its  fibrillar  structure  only  with  special  methods. 
Frequently  the  protoplasm  contains  pigment  granules.  The  "reticular 
apparatus"  is  said  to  be  present  always,  and  slender  intracellular  canals 
(trophospongium)  have  been  described  (Figs.  5  and  6,  p.  4).  Fine- 
meshed  reticular  networks  have  been  found  covering  the  exterior  of  the 
nerve  cells,  and  they  have  been  ascribed  both  to  the  terminal  ramification 
of  nerve  fibers  and  to  branches  of  the  supporting  tissue.  A  ganglion  cell 
is  often  surrounded  by  flat  or  stellate  cells  arranged  in  concentric  layers 
so  as  to  form  a  sheath.  Within  the  sheath  there  is  a  homogeneous  mem- 
brane or  capsule,  on  the  inner  side  of  which  are  cells  arranged  in  a  single 
layer,  corresponding  to  the  cells  within  the  neurolemma  of  peripheral 


148 


HISTOLOGY 


nerves.     Connective  tissue,  containing  small  blood  vessels,  passes  be- 
tween the  ensheathed  cells  of  the  ganglion. 

In  the  embryo  the  cells  of  the  spinal  ganglia  are  bipolar,  but  generally 
they  become  unipolar,  with  T-shaped  processes,  as  already  described. 
In  the  ganglia  of  the  acoustic  nerve,  however,  the  bipolar  form  is  said  to 
be  retained,  and  these  cells  are  not  surrounded  by  capsule  or  "mantle" 
cells.  In  other  ganglia  of  the  cerebral  nerves,  and  in  spinal  ganglia,  the 
cells  are  arranged  as  shown  in  the  diagram,  Fig.  135.  Their  branches 
can  be  studied  only  in  special  preparations,  made  usually  by 
Ehrlich's  methylene  blue  method,  or  CajalY  silver  nitrate  method. 


Cross  section  of  a  medullated  nerve  fiber. 


Nucleus  of  the 
capsule 


Longitudinal  view 
of  medullated 
nerve  fibers.  Surface  view  of 

nucleated  sheath. 

FIG.  134. — FROM  A  CROSS  SECTION  OF  A  HUMAN  SEMILUNAR  GANGLION.     X  240. 

At  x  the  beginning  of  a  protoplasmic  process  has  been  included  in  the  section;  elsewhere  the  processes 

cannot  be  seen. 

The  most  characteristic  cells  (Fig.  135,  3)  have  large  round  bodies 
and  a  single  spirally  coiled  process,  which  arises  from  a  conical 
projection  of  the  protoplasm.  The  process  often  winds  about  the 
cell  body.  Soon  after  passing  through  the  capsule  it  acquires  a  sheath 
of  myelin,  and  is  covered  with  neurolemma.  It  may  give  off  collaterals  be- 
fore it  divides  into  its  two  main  branches,  which  correspond  with  dendrite 
and  neuraxon  respectively.  Sometimes  the  process  divides  into  three 
branches  (Fig.  135,  2);  the  branching  takes  place  at  a  node  of  Ranvier. 
Certain  of  the  large  cells,  as  found  constantly  in  the  human  jugular  gang- 
lion, lack  the  coiled  windings,  so  that  the  process  passes  directly  through 
the  capsule  and  divides  at  once  into  its  two  branches. 

Frequently  the  ganglion  cells  are  provided  with  short  processes  which 
end  in  rounded  enlargements,  either  within  the  capsule  (Fig.  135,  5)  or 
outside  of  it  (Fig.  135,  6).  Collateral  branches  may  end  in  this  way. 


NERVOUS    TISSUE 


149 


These  "end  discs"  were  first  observed  by  Huber  in  frogs  (Anat.  Ariz., 
1896,  vol.  12,  pp.  417-425).  They  are  found  not  only  in  spinal  ganglia, 
but  also  in  the  central  nervous  system  and  in  sympathetic  ganglia;  and, 


Motor  cell  of 
the  spinal  cord. 


Ventral 
root. 


Dorsal  root. 


Spinal 
ganglion. 


End  disc 


Capsule. 


ramus.     Dorsal 
ramus. 


FIG.  135. — DIAGRAM  OF  THE  NERVOUS  ELEMENTS  IN  A  HUMAN  SPINAL  GANGLION. 

after  the  distal  part  of  a  nerve  has  been  cut  away,  the  axis  cylinders  of  the 
proximal  part  send  out  many  such  buds,  which  grow  into  the  myelin 
toward  the  place  of  injury.  In  all  cases  they  are  regarded  as  abortive 


150  HISTOLOGY 

branches.  They  are  said  to  occur  normally  only  in  adults,  and  especially 
in  old  age,  being  very  numerous  in  the  nodose  ganglion  of  the  vagus 
nerve. 

Another  feature  which,  in  man,  has  been  found  almost  exclusively 
in  the  nodose  ganglion  of  adults,  is  the  occurrence  of  "fenestrated  cells." 
These  are  ganglion  cells  with  peripheral  vacuoles,  which  may  break  down 
so  that  the  cell  appears  multipolar  (Fig.  135,  7).  Sometimes  they  are  so 
arranged  that  the  cell  process  seems  to  grow  out  by  several  roots  (Fig. 
135,  8).  Although  the  fenestrated  cells  increase  in  number  with  advancing 
age,  they  are  not  considered  pathological,  since  they  occur  in  young  dogs 
and  other  animals. 

Less  conspicuous  than  the  large  cells  with  medullated  fibers,  but  more 
numerous,  are  small  pyriform  cells  with  non-medullated  fibers  (Fig.  135, 
4).  Ranson,  from  his  own  and  previous  observations,  concludes  that  in 
the  cat  and  rat,  in  which  the  cells  have  been  carefully  counted,  about 


Nerve  cell. 
\ 


Sheath.  Sheath. 

A  B 

FIG.  136. — CELLS  OF  THE  HUMAN  SYMPATHETIC  GANGLIA.     (Prepared  by  L.  R.  Mullet.)      X  465- 
A,  From  the  ciliary  ganglion;  B,  from  the  superior  cervical  ganglion. 

two-thirds  of  the  spinal  ganglion  cells  may  be  classified  as  small,  and  are 
associated  with  non-medullated  fibers  (Amer.  Journ.  of  Anat.,  1911,  vol. 
12,  pp.  67-87). 

The  spinal  ganglion  cells  are  sometimes  surrounded  by  fine  networks 
of  non-medullated  fibers,  which  are  probably  the  terminal  branches  of 
medullated  fibers  derived  from  cells  in  the  sympathetic  ganglia  (Fig.  135, 
i).  Branches  of  the  sympathetic  fibers  are  also  distributed  to  the  blood 
vessels  in  the  ganglion.  Whether  any  fibers  pass  through  the  spinal 
ganglion  without  connecting  with  its  nerve  cells  is  still  uncertain;  they  have 
not  been  demonstrated  in  mammals. 

Sympathetic  Ganglia.  The  sympathetic  ganglia  consist  of  multipolar 
cells  which  are  smaller  than  those  of  spinal  ganglia  (Fig.  136).  Their 
round  or  oval  nuclei,  often  eccentric,  have  prominent  nucleoli  and  a  loose 
chromatin  network,  as  in  other  nerve  cells;  some  of  them  contain  two 


NERVOUS    TISSUE 


nuclei.  The  protoplasm  is  often  pigmented.  Around  the  cell  bodies, 
nuclei  of  the  sheath  cells  may  be  abundant.  Three  types  of  sympathetic 
ganglion  cells  are  shown  in  Fig.  137.  The  motor  cells,  terminating  in 
contact  with  smooth  muscle  fibers,  are  by  far  the  most  abundant  (Fig. 
137,  i).  Their  neuraxons  are  non-medullated  fibers,  which  are  provided 
with  very  slender  collaterals.  The  cell  body  is  stellate  and  its  branching 
dendrites  appear  spiny.  The  second  type  (Fig.  137,  2)  is  possibly  sensory, 


Motor  fiber  from  a  spinal  nerve. 
\ 

Pericellular  plexus. 


Capsule 


Neuraxons.- — ^- Y  £jfe|i 


Sympathetic  // .', 

nerve.  ^ 


Sensory  fiber  from 
spinal  nerve. 


Sympathetic  (?) 
nerve  fiber. 


Section  of  the 

pericapsular 

plexus. 

Surface  view 

of  pericapsular 

plexus. 


Stellate  cell. 


Neuraxon. 


Smooth 
muscle  fibers. 


Lamellar  corpuscle. 


FIG.  137. — DIAGRAM  OF  THE  ELEMENTS  OF  Two  SYMPATHETIC  GANGLIA. 

but  the  terminations  of  its  fibers  are  not  known.  Its  dendrites  are  long 
and  slender  and  may  extend  from  one  ganglion  to  another.  Some  of  them 
are  accompanied  by  the  neuraxon,  which  may  acquire  a  medullary  sheath, 
often  at  a  considerable  distance  from  the  cell  body.  Cells  of  the  third 
type  (Fig.  137,  3)  resemble  those  of  the  second  type.  They  have  long 
branching  dendrites  which  pass  between  the  adjacent  cells  to  the  periphery 
of  the  ganglion,  where  they  form  a  plexus.  Their  non-medullated  neurax- 


152  HISTOLOGY 

ones  pass  out  of  the  ganglion,  but  their  terminations  are  unknown.  Small 
stellate  cells,  one  of  which  is  shown  in  the  figure,  presumably  belong  with 
the  supporting  tissue. 

Fibers  from  the  spinal  nerves  may  pass  through  the  sympathetic 
ganglia,  or  terminate  within  them.  Thus  spinal  motor  fibers,  after 
losing  their  myelin  sheaths,  form  pericellular  plexuses  about  the  sym- 
pathetic motor  cells,  and  their  collaterals  end  in  the  same  way.  They 
are  apparently  indistinguishable  from  the  sympathetic  fibers  which  pass 
from  one  ganglion  to  another  and  terminate  in  pericellular  networks. 
Medullated  sensory  fibers,  some  of  which  arise  from  lamellar  corpuscles, 
extend  through  the  sympathetic  nerves  to  enter  the  spinal  ganglia. 

Chromaffin  organs,  or  paraganglia,  are  masses  or  cords  of  cells  which 
originate  in  close  association  with  sympathetic  ganglia.  Although  they 
have  often  been  classed  with  nervous  tissue,  they  are  to  be  regarded  as 
glands  which  produce  an  internal  secretion.  This  secretion  acts  upon  the 
smooth  musculature  in  the  walls  of  the  blood  vessels  and  causes  it  to 
maintain  a  proper  state  of  contraction,  or  tonus. 

When  fresh,  chromarnn  tissue  is  darkly  colored.  If  preserved  in  fluids 
containing  chromic  acid  or  salts  of  chromium,  the  cells  which  contain 
secretion  acquire  a  yellowish-brown  stain.  The  term  chromqffi-n  refers 
to  this  specific  affinity  for  chromium,  and  does  not  mean  that  the  cells 
stain  deeply. 

Groups  of  chromaffin  cells  are  found  in  connection  with  the  ganglionated 
trunk  of  the  sympathetic  system.  In  the  new-born  child  these  "  chromaf- 
fin bodies"  may  reach  a  length  of  1-1.5  mm.  (Zuckerkandl)  and  several 
of  them  may  be  associated  with  a  single  ganglion.  They  are  always  found 
in  the  plexus  at  the  bifurcation  of  the  carotid  artery,  where  they  enter 
into  the  formation  of  the  carotid  gland  (glomus  caroticum).  They  occur 
in  varying  number  sin  the  cceliae,  renal  and  hypogastric  plexuses,  and  extend 
along  the  vessels  so  that  chromaffin  cells  are  found  in  relation  with  the 
kidneys,  ureters,  prostate,  epididymis  and  ovary.  The  largest  bodies 
(the  organs  of  Zuckerkandl)  are  found  on  either  side  of  the  inferior  mesen- 
teric  artery,  and  may  connect  with  one  another  by  a  bridge  across  the 
front  of  the  aorta.  At  birth  "the  average  length  of  the  right  one  is  n.6 
mm.,  and  of  the  left,  8.8  mm."  Usually  there  are  two  chromarfin  bodies 
on  either  side  in  the  hypogastric  plexus,  but  the  total  number  of  bodies 
connected  with  the  abdominal  plexuses  varies  greatly,  "from  7  to  26,  or 
even  more;  in  one  case  nearly  70"  (Zuckerkandl).  Although  they  undergo 
regressive  changes  after  birth,  they  do  not  dissappear. 

The  medulla  of  the  suprarenal  glands  consists  of  chromaffin  tissue, 
which  has  very  important  functions  throughout  life;  it  will  be  described 
in  connection  with  the  suprarenal  glands. 


NERVOUS    TISSUE 


153 


STRUCTURE   OF   NERVES. 

Nerves  are  bundles  of  nerve  fibers  passing  between  the  central  nervous 
system  and  the  various  parts  of  the  body;  they  are  so  widely  distributed 
that  they  may  be  found -in  sections  of  most  of  the  organs  and  tissues. 
When  examined  fresh,  in  reflected  light,  nerves  are  seen  to  be  of  two  sorts, 
formerly  known  as  white  and  gray  nerves,  respectively.  Similarly,  sec- 
tions of  the  brain  and  spinal  cord  are  formed  of  white  substance  and  gray 
substance.  The  obvious  distinction  in  color  is  due  to  the  presence  or 
absence  of  microscopic  sheaths  of  myelin  around  the  individual  fibers. 
Nerves  which  contain  a  large  proportion  of  myelinated  or  medullated 
fibers  are  white;  and  those  which  have  few  are  gray.  All  nerve  fibers 
when  first  formed  are  non-medullated,  and  most  of  the  sympathetic  nerves 
remain  in  this  condition. 

Non-medullated  nerves  can  readily  be  found  between  the  circular  and 
longitudinal  layers  of  smooth  muscle  in  any  part  of  the  digestive  tube. 
They  are  circumscribed  bundles  of  fine  fibers  running  through  the  coarser 
connective  tissue  (Fig.  138).  Many  of  them  contain  nerve  cells,  unmis- 


FIG.  138. — A  SYMPATHETIC  NERVE  FROM  THE  MYENTERIC  PLEXUS  OF  A  CAT.     X  775- 

a.,  Nucleus  of  a  supporting  cell;  b.,  nerve  cell;  c.,  non-medullated  nerve  fibers.     Above  the  nerve  are  cir- 
cular smooth  muscle  fibers  in  longitudinal  section;  below  it  are  longitudinal  fibers  in  cross  section. 

takably  characterized  by  large,  round  or  oval,  vesicular  nuclei,  having  a 
prominent  nucleolus.  Around  the  nucleus  is  dense  protoplasm,  starting 
out  in  branching  processes,  all  but  the  roots  of  which  are  cut  away  in 
sectioning.  Other  cells  are  found,  having  relatively  small  nuclei  and  very 
indefinite  or  wholly  imperceptible  protoplasmic  bodies.  These  are  support- 
ing cells;  they  produce  a  syncytial  framework  in  which  the  nerve  cells 
and  their  very  delicate  ramifications  are  imbedded.  The  framework 
tends  to  form  septa,  subdividing  the  nerve  into  smaller  bundles. 

Some  non-medullated  fibers,  but  by  no  means  all,  are  closely  invested 
by  sheath  cells.  According  to  Schafer,  the  nuclei  of  these  cells  appear  to 
be  interpolated  in  the  substance  of  the  fiber,  and  it  is  impossible  to  demon- 


154 


HISTOLOGY 


strate  a  distinct  sheath  (Fig.  139).  Similarly  Bar deen  has  stated  that  it 
is  "  mainly  a  matter  of  judgment  to  decide  whether  the  fibrils  are  sur- 
rounded by  or  imbedded  within  the  sheath  cells."  They  correspond  with 
the  neurolemma  cells  of  medullated  nerves. 

Medullated  Nerves.  The  larger  sympathetic  nerves  contain  a  consider- 
able number  of  medullated  fibers,  and  the  splanchnic  nerves  are  described 
as  white.  In  the  trunks  of  the  spinal  nerves,  however,  the  medullated 
fibers  attain  their  maximum  development.  Examined  with  low  magnifi- 


FIG.  139. — NON-MEDULLATED  NERVE  FIBERS.     X  400.     (After  Schafer.) 

cation,  such  a  nerve  is  seen  to  consist  of  round  cords  imbedded  in  loose 
connective  tissue  (Fig.  140).  This  loose,  tissue,  which  surrounds  the 
entire  nerve  and  its  several  cords,  is  the  epineurium;  its  connective  tissue 
bundles  are  chiefly  longitudinal,  and  are  associated  with  abundant  elastic 
tissue  and  frequent  fat  cells;  it  contains  the  blood  vessels  which  supply 
the  nerve.  Each  cord  is  surrounded  by  a  dense  lamellar  layer  of  connect- 
ive tissue,  which  contains  flattened  cells  in  contact  with  one  another  so 
that  they  form  more  or  less  continuous  membranes.  This  layer  is  the 


Fat  cells. 


Artery. 


Bundles  of  nerve  fibers. 


Epineurium. 


Perineurium. 


Endoneurium. 


FIG.  140.— MEDULLATED  NERVE.     PART  OF  A  CROSS  SECTION  OF  THE  HUMAN  MEDIAN  NERVE.     X  20. 

perineurium.  It  is  continuous  with  the  outer  membranes  covering  the 
cord,  and  contains  cleft-like  spaces  which  are  said  to  communicate  with 
the  subdural  and  subarachnoid  spaces,  but  which  do  not  connect  with 
lymphatic  vessels  in  the  epineurium.  Prolongations  of  the  perineurium 
extend  as  septa  into  the  larger  nerve  bundles  and  constitute  the  endoneu- 
rium,  which  may  penetrate  between  the  individual  nerve  fibers,  forming 
the  so-called  "sheaths  of  Henle."  Their  nuclei  are  always  outside  the 
neurolemma. 


NERVOUS   TISSUE 


155 


The  individual  nerve  fibers  vary  in  diameter,  and  the  larger  ones  are 
probably  those  which  have  a  longer  course.  It  is  impossible  to  distin- 
guish histologically  between  sensory  and  motor  fibers.  The  sheath  of 


Medullary 
sheath. 


Endo- 
neurium. 


Fiber  sheath. 


FIG.  141. — MEDULLATED  NERVE.     PART  OF  A  CROSS  SECTION  OF  THE  HUMAN  MEDIAN  NERVE.    X  220. 

myelin  which  surrounds  the  fiber  varies  greatly  in  thickness,  as  seen 
in  the  cross  section,  Fig.  141.  In  ordinary  preparations  it  forms  light 
zones  around  the  dark  fibers,  suggesting  the  relation  between  protoplasm 
and  nucleus;  but  the  rod-like  nature  of  the  central  fibers  is  evident  on 
changing  the  focus.  The  myelin  is  sur- 
rounded by  the  membranous  neurolemma, 
within  which  the  single  internodal  nucleus 
is  occasionally  included  in  a  given  section. 
Portions  of  isolated  fibers,  viewed  longi- 
tudinally, are  shown  in  Fig.  142. 


N 


FIG.    142. — Two 


M 


N 


Myelin  is  a  mixture  of  complex  fats  and  lipoid 
substances,  some  of  which  are  combined  with 
sugar.  Like  fat,  it  is  dissolved  by  ether  and 
blackens  with  osmic  acid.  In  preserved  speci- 
mens the  emulsion  breaks  down,  giving  rise  to 
various  forms  of  shrinkage.  A  network  which 
appears  after  fibers  have  been  treated  with 
alcohol  and  ether  is  said  to  be  composed  of 
neurokeratin,  a  substance  insoluble  in  these 
reagents,  which  does  not  blacken  with  osmic 
acid.  The  size  of  the  meshes  varies  (Fig.  143, 
A,  B).  In  preparations  blackened  with  osmic 
acid,  the  myelin  is  often  traversed  by  oblique 
clefts,  the  incisures  of  Lantermann  (Fig.  143,  D). 
The  arrangement  of  these  characteristic  clefts 
may  be  pictured  by  imagining  a  succession  of  stemless  funnels  strung  along  the 
axis  cylinder,  not  all  of  which  are  pointed  the  same  way.  The  incisures  are  doubt- 
less artificial,,  and  their  number  is  increased  by  pulling  the  nerve  fibers  apart;  they 
appear  to  be  empty  or  crossed  by  strands  of  myelin,  but  in  the  preparation  shown  in 


Nu. 


NERVE  FIBERS  WITH 
SHRUNKEN  Axis  CYLINDERS  FROM 
THE  SCIATIC  NERVE  OF  A  RABBIT. 
X  350. 

A,  Axis  cylinder;  M,  medullary  sheath 
(myelin);  N,  neurolemma;  Nu,  nu- 
cleus of  the  neurolemma. 


156 


HISTOLOGY 


Fig.  143,  C,  the  neurokeratin  framework  is  so  arranged  as  to  correspond  with  these 
intervals.  In  transverse  sections,  incisures  are  included  in  Fig.  143,  E  and  I;  the 
concentric,  vacuolated  and  radial  appearances  of  the  myelin  are  represented  in  F-H. 

The  nodes  of  Ranvier,  shown  in  the  diagram,  Fig.  131,  are  conspicuous  in  isolated 
nerve  fibers  stained  with  osmic  acid.  Various  interpretations  of  their  structure  are 
represented  in  Fig.  144.  According  to  the  first  (Fig.  144,  A)  the  myelin  occurs 
like  fat,  within  distinct  cells  wrapped  around  the  nerve  fibers;  the  node  is  the  interval 
between  successive  cells.  The  nucleus,  which  is  flattened  by  the  myelin  against 
the  outer  cell  wall,  mid- way  between  the  nodes,  is  not  shown.  Corresponding  with 
the  neurolemma  on  the  outside,  there  is  an  "axolemma"  next  the  axis  cylinder; 
neurolemma  and  axolemma  come  together  at  the  node.  If  the  nerve  fibers  are  treated 
with  silver  nitrate,  a  black  precipitate  is  produced  at  the  nodes,  as  if  an  intercellular 
substance  were  present;  the  blackening  may  extend  up  the  axis  cylinder  producing 
cross-shaped  figures  (Fig.  144,  B). 


my 


FIG.  143. — MEDULLATED  NERVE  FIBERS. 
A-D,  Longitudinal  sections;  E-I,  cross  sections. 
(A-B,  after  Gedoelst;  C,  E,  F,  after  Hardesty;  D 
and  I,  osmic  acid  preparations,  after  Prenant 
and  Scymonowicz;  G,  alcoholic  preservation, 
after  Koelliker  H,  picric  acid  preservation,  after 
Schafer.)  a.  c.,  Axis  cylinder;  in.,  incisure;  my., 
myelin;  nu.,  nucleus  of  the  neurolemma. 


no 


FIG.  144. — NODES. 

A,  Diagram  of  the  intracellular  explanation 
of  myelin;  B,  the  cross  obtained  with 
silver  nitrate;  C,  the  biconical  enlarge- 
ment (after  Gedoelst);  D,  intercellular 
myelin  (after  Hardesty);  a.  c.,  axis  cylin- 
der; ax.,  axolemma;  my.,  myelin;  ne., 
neurolemma;  no.,  node. 


As  the  axis  cylinder  traverses  the  node,  its  fibrils  may  spread  apart,  forming  a 
"biconical  enlargement."  The  fibrils  in  the  midst  of  the  enlargement  have  been 
described  as  thickened  (Fig.  144,  C).  The  same  figure  shows  no  axolemma  and 
suggests  that  the  neurolemma  passes  across  the  node  without  interruption.  This 
is  clearly  shown  in  D,  where  the  myelin  layer  also,  though  constricted,  is  not  com- 
pletely divided.  The  myelin  has  accordingly  been  regarded  as  an  exoplasmic  part 
of  the  axis  cylinder,  and  chemically  it  is  said  to  be  related  to  the  interfibrillar  substance 
or  neuroplasm.  Bardeen  (Amer.  Journ.  Anat.,  1903,  vol.  2,  pp.  231-257)  considers 
that  the  myelin  is  derived  from  the  intercellular  substance  between  the  fiber  and  the 
sheath,  and  is  "due  to  influences  exerted  by  the  axis  cylinder  fibrils."  That  the 
axis  cylinder  plays  the  chief  part  in  its  production  is  indicated  by  the  fact  that  the 
myelin  breaks  down  when  the  fiber  degenerates,  and  that  it  forms  around  fibers  in  the 
central  nervous  system  where  there  are  no  continuous  sheaths. 

The  production  of  myelin  is  said  to  begin  at  about  the  fourth  month,  at  the  central 
ends  of  the  nerves.  It  begins  at  different  times  in  different  tracts  and  systems,  and 


NERVOUS    TISSUE 


157 


the  medullary  sheaths  of  the  spinal  nerves  are  not  all  formed  until  two  or  three  years 
after  birth.     They  continue  to  increase  in  thickness  into  adult  life. 


NERVE   ENDINGS. 

SENSORY  ENDINGS.     The  outward  growth  of  nerve  fibers  from  cells 
in  the  ganglia  of  the  spinal  and  cerebral  nerves  has  already  been  described. 
Near  their  terminations  these  fibers  branch  repeatedly  at  the  nodes,  lose 
their  myelin  sheaths,  and  form  terminal  arboriza- 
tions in  contact  with  epithelial,  connective  tissue,  or 
muscle  cells.     These  are  the  sensory  endings,  and 
apart  from  those  connected  with  the  eye,  ear,  and 
other  organs  of  special  sense,  they  may  be  described 
as  follows. 

Free  Endings.  Sensory  fibers  to  the  epidermis 
and  to  the  corneal  and  oral  epithelia  penetrate  the 
basal  layer,  passing  between  the  cells  as  unsheathed 
fibers,  and  ramify  among  the  cells  in  the  outer  layers 
(Fig.  145).  The  extremities  of  the  fibers,  which  may  be  pointed  or 
club-shaped,  are  in  contact  with  the  epithelial  cells,  but  do  not  enter 
them.  In  the  process  of  branching  the  neurofibrils  become  distributed 


FIG. 


145. — FREE  NERVE 
ENDING,  IN  EPITHE- 
LIUM. GOLGI  PREP- 
A  R  A  T  i  o  N  .  (After 
Retzius.) 


Intraepithelial      nerve 
fiber. 


Papilla. 


Capillaries. 


Tactile  cells. 


Tactile 
meniscus. 


Corium. 


FIG.  146. 


Tactile  cells  Nerve  fiber, 

in  the  corium. 

FIG.  147. 


FIGS.  146  AND  147. — FROM  VERTICAL  SECTIONS  THROUGH  THE  SKIN  OF  THE  GREAT  TOE  FROM  A  MAN  OF 

TWENTY-FIVE  YEARS.     X  360. 

in  smaller  and  smaller  bundles,  which  often  anastomose,  forming  plexuses; 
but  whether  the  interlacing  constituent  fibrils  unite  with  one  another  so 
as  to  form  a  net  has  been  questioned.  At  the  ends  of  the  branches,  each 


158 


HISTOLOGY 


fibril  has  become  separate  from  the  others;  frequently  it  shows  varicose 
enlargements. 

Free  sensory  endings  occur  not  only  in  stratified  epithelia,  but  also  in 


Medullated 
nerves. 
A 


""Medullated  nerve  fiber. 


Terminal  ramification.     Tendon  bundle. 


Muscle  fibers. 

i\ 


FIG.  149. — TENDON  SPINDLE  OF  AN  ADULT  CAT.     X  80. 


•  -X .  -.-' 

:\ 


~ •  Medullated  nerve  fiber. 

""    Axis  cylinder. 

—  Nucleus  of  a  tendon  eel! 


FIG.  150.— THE  LEFT  PORTION  OF  FIG.  149.     X  345- 


muscle,  tendon  and  connective  tissue.  In  simple  epi- 
thelia the  free  endings  may  be  sensory,  but  in  glandular 
epithelia  they  are  often  efferent  fibers,  inciting  the  cells 
to  glandular  activity.  The  ultimate  branches  of  the 
nerves  are  so  delicate  that  they  cannot  be  seen  in 
ordinary  preparations;  they  have  been  demonstrated 
chiefly  by  the  methylene  blue  method,  applied  to  very 
fresh  or  living  tissue. 

In  the  epidermis,  as  a  modification  of  the  free  end- 
ings, fibers  are  found  terminating  in  disc-shaped  net- 
works (tactile  menisci)  at  the  base  of  modified  cells  (Fig.  147).  These 
tactile  cells  may  occasionally  be  seen  in  ordinary  preparations. 


FIG.  148. — MUSCLE 
SPINDLE  OF  AN 
ADULT  CAT.  X 135. 


NERVOUS    TISSUE 


159 


The  stellate  "Langerhans  cells"  shown  in  Figs.  146  and  147  are  usually 
regarded  as  wandering  cells  lodged  in  intercellular  spaces,  but  Stohr  states 
that  intergrading  forms  connect  them  with  the  epithelial  cells;  and  they 
may  act  as  sensory  cells. 

Muscle  Spindles.  As  seen  in  ordinary  preparations  muscle  spindles 
are  shown  in  Fig.  119  (p.  127).  They  are 
slender  groups  of  3-20  muscle  fibers,  1-4  mm. 
long  and  0.08-0.2  mm.  wide,  around  which 
nerve  fibers  terminate  as  shown  in  Fig.  148. 
The  spindles  are  surrounded  by  a  thick  connec- 
tive tissue  sheath  or  capsule,  continuous  with 
the  perimysium,  and  said  to  be  divided  into  an 
•—ft  inner  and  an  outer  layer  by  a  space  filled  with 
fluid.  The  muscle  fibers  of  the  spindle  are 
poorly  developed.  They  are  distinctly  striated 
toward  their  tapering  and  very  slender  ends, 
but  in  their  middle  portions,  sarcoplasm  and 
nuclei  are  abundant  and  the  striations  ill  de- 
fined. Three  or  four  nerves  terminate  in  each 
spindle.  Their  connective  tissue  sheaths  blend 
with  the  perimysial  capsule,  and  they  branch 


Tactile  cells, 


il 


Nerve  fibrils. 


Connective  tis- 
sue sheath. 


FIG.      151. — TERMINAL     CYLINDER. 

(After  Ruffini,  from   Ferguson's 

Histology.) 
gH,  Medullary   sheath;   il,   terminal 

ramifications  of  the  axis  cylinder; 

L,  connective  tissue. 


FIG.  152. — TACTILE  CORPUSCLE  FROM  A  SECTION  OF  THE  SKIN 

OF  A  HUMAN  FINGER.     X  560. 
(Prepared  by  van  der  Velde,  after  the  Bielschowsky  method.) 


and  lose  their  myelin  as  they  pass  through  it  to  the  muscle  cells. 
They  may  encircle  the  muscle  fibers  of  the  spindle,  forming  spirals  or 
rings  (as  in  the  upper  part  of  Fig.  148),  or  they  may  form  a  panicle  of 
branches  with  enlarged  club-shaped  ends.  Since  they  do  not  degenerate 
after  the  motor  roots  have  been  cut,  they  are  supposed  to  be  sensory 
fibers,  but  their  function  has  not  been  established.  Other  sensory  fibers 
to  muscle  have  free  endings,  as  shown  in  Fig.  157. 


i6o 


HISTOLOGY 


Tendon  Spindles.  Tendons  possess  free  sensory  endings,  together 
with  the  tendon  spindles.  These  are  small  portions  of  the  tendon,  1-3 
mm.  long  and  0.17-0.25  mm.  wide,  enclosed  in  sheaths  of  connective 
tissue.  They  stain  more  deeply  than  the  surrounding  tendon. 

The  few  nerve  fibers  which  terminate  in  a  tendon  spindle  lose  their 
sheaths  and  branch  freely,  ending  in  club-shaped  enlargements  (Figs.  149 
and  150).  They  are  found  in  all  tendons  and  serve  to  transmit  the  sensa- 
tion of  tension,  being  active  in  connection  with  coordinated  movements. 

In  connective  tissue  the  sensory  nerves  may  have  free  endings.  In 
addition  to  these  the  subcutaneous  tissue  near  the  coils  of  the  sweat 

glands,  and  in  the  corium  of  the  fingers 
and  toes,  sometimes  contains  terminal 
cylinders  (of  Ruffini)  which  resemble 
tendon  spindles  in  the  way  that  their 
nerves  ramify  (Fig.  151).  These  cylin- 
ders lack  the  distinct  capsules  which 
characterize  the  nerve  corpuscles. 


FIG.  153. — GENITAL  CORPUSCLE  FROM?THE 
HUMAN  GLANS  PENIS.  METHYLENE 
BLUE  STAIN.  (After  Dogiel,  from  Bohm 
and  von  Davidoff.) 


FIG.  154. — BULBOUS  CORPUSCLE  FROM  THE  HUMAN  CON- 
JUNCTIVA. METHYLENE  BLUE  STAIN.  (After  Dogiel, 
from  Bohm  and  von  Davidoff.) 


Terminal  corpuscles  are  nerve  endings  consisting  of  a  coarse  nerve 
fiber,  or  knot  of  small  branches,  surrounded  by  a  semifluid  intercellular 
substance  (which  is  granular  in  preserved  tissue),  and  enclosed  in  a  con- 
nective tissue  capsule.  The  terminal  ramifications  of  the  nerve  show 
irregular  swellings  or  varicosities,  arid  apparently  they  unite  so  as  to  make 
a  network.  Often  more  than  one  fiber  enters  a  corpuscle,  and  it  has  been 
suggested  that  they  include  afferent  and  efferent  firjers.  Generally  the 
connective  tissue  sheaths  of  the  entering  fibers  blend  with  the  capsule, 
and  the  myelin  sheaths  are  lost  just  within  it.  Terminal  corpuscles  have 
been  grouped  as  tactile,  genital,  bulbous,  articular,  cylindrical,  and  lamellar. 

Tactile  corpuscles  (or  Meissner's  corpuscles)  are  elliptical  structures, 
40-100  /*  long  and  30-60  n  broad  (Fig.  152).  They  are  characterized 
by  transverse  markings,  due  to  the  corresponding  elongation  of  the  capsule 
cells  and  the  tactile  cells  within.  From  one  to  five  medullated  fibers 
enter  the  lower  end  of  a  tactile  corpuscle,  losing  their  sheaths  soon  after 
entering.  They  pursue  a  spiral  course  through  the  corpuscle,  giving  off 


NERVOUS    TISSUE 


161 


FIG.  155. — CYLINDRICAL  CORPUSCLES,  FROM  INTER- 
MUSCULAR    SEPTUM    OF    CAT.     METHYLENE 


branches  which  end  in  enlarged  terminal  networks  between  and  upon  the 
tactile  cells.  These  corpuscles  are  found  in  some  of  the  papillae,  or  con- 
nective tissue  elevations  just  beneath  the  epidermis,  being  especially 
numerous  in  those  of  the  soles  and  palms  (23  in  i  sq.  mm.)  and  in  the 
finger  tips;  they  occur  also  "in  the  nipple,  border  of  the  eyelids,  lips, 
glans  penis  and  clitoris." 

Genital  corpuscles  are  large,  round 
or  oval  bodies  60-400  julong  (Fig.  153) 
which  may  receive  as  many  as  ten 
nerve  fibers.  These  ramify  and  send 
branches  to  neighboring  corpuscles, 
and  also  to  the  epidermis.  The  gen- 
ital corpuscles  are  deeply  placed  be- 
neath the  epithelium  of  the  glans 
penis,  clitoris,  and  adjoining  structures. 

Bulbous  corpuscles  (of  Krause)  are  smaller  than  the  genital  corpuscles, 
having  a  diameter  of  20-100  /*  (Fig.  154).  They  are  most  numerous 
(1-4  in  a  sq.  mm.)  in  the  superficial  connective  tissue  of  the  glans  penis 
and  clitoris.  Similar  structures,  either  round  or  oval,  are  found  in  the 
conjunctiva  and  "edge  of  the  cornea,  in  the  lips  and  lining  of  the  oral 
cavity,  and  probably  in  other  parts  of  the  corium."  They  have  thinner 

capsules  and  receive  fewer  nerves  than 
the  genital  corpuscles,  which  they  re- 
semble. The  articular  corpuscles,  found 
near  the  joints,  belong  in  the  same 
category. 

Cylindrical  corpuscles  (cylindrical 
end  bulbs  of  Krause)  contain  a  single 
axial  nerve  fiber  with  few  or  no  branches, 
terminating  in  a  knob-like  or  rounded 
extremity  (Fig.  155).  The  fiber  is  sur- 
rounded by  a  semi-fluid  substance, 
sometimes  described  as  an  inner  bulb, 
and  this  is  enclosed  in  a  few  concentric 
layers  of  cells  which  are  continuous 
with  the  sheath  of  the  nerve.  Cylin- 
drical corpuscles  are  found  in  the 
mucous  membrane  of  the  mouth  and  in  the  connective  tissue  of  muscles 
and  tendons. 

Lamellar  corpuscles  (or  Pacinian  corpuscles)  are  macroscopic  elliptical 
structures  0.5-4.5  mm.  long  and  1-2  mm.  wide  (Fig.  156).  They  were 
first  observed  in  dissections,  as  minute  vesicular  bodies  attached  to  the 
terminal  branches  of  nerves.  Microscopically  they  are  striking  objects, 


Axis  cylinder. 


Inner  core. 


FIG.  156. — SMALL  LAMELLAR  CORPUSCLE 
FROM  THE  MESENTERY  OF  A  CAT.  X  so. 

The  nuclei  of  the  capsule  cells  appear  as 
thickenings.  The  myelin  of  the  nerve 
fiber  may  be  traced  to  the  inner  core. 


l62 


HISTOLOGY 


suggesting  an  encysted  foreign  body.  The  axial  core  of  the  corpuscles 
is  surrounded  by  concentric  layers,  sometimes  as  many  as  fifty,  which 
represent  a  perineurium  distended  with  fluid.  A  single  large  nerve  fiber 
enters  one  end  of  the  corpuscle  and  loses  its  myelin  as  it  traverses  the 
lamellae.  It  extends  through  the  semifluid  core  without  obvious  branches, 
sometimes  being  flattened  and  band-like;  it  may  fork  at  its  further  end 
or  form  a  coil  of  branches,  and  it  has  been  observed  to  pass  out  and  enter 
another  such  corpuscle.  Usually  the  corpuscles  are  sectioned  obliquely 
or  transversely  so  that  the  concentric  layers  completely  encircle  the  inner 
core. 

Special  methods  have  shown  that  the  axial  fiber  may  possess  many 
short  lateral  branches  ending  in  knobs,  and  that  one  or  more  delicate 
fibers  may  enter  (or  leave)  the  corpuscles  in  addition  to  the  large  one  just 


Sensory  nerve  fibers 
Muscle  fibers 

Motor  plate 


Medullated  nerve  fibers/] 

I 
I 


Nerve  fiber  bundle 


FIG.  157. — MOTOR  NERVE  ENDINGS  OF  INTERCOSTAL  MUSCLE  FIBERS  OF  A  RABBIT.     X    150. 


described;  they  form  a  net  surrounding  the  axial  fiber.  A  small  artery 
may  pass  into  the  corpuscle  beside  the  nerve  and  supply  the  lamellae 
with  capillaries.  Lamellar  corpuscles  are  abundant  in  the  subcutaneous 
tissue  of  the  hand  and  foot  and  occur  in  other  parts  of  the  skin,  in  the 
nipple,  and  in  the  territory  of  the  pudendal  nerve;  they  are  found  near 
the  joints  (particularly  on  the  flexor  side)  and  in  the  periosteum  and  peri- 
mysium,  in  the  connective  tissue  around  large  blood  vessels  and  nerves, 
and  in  the  tendon  sheaths;  also  in  the  serous  membranes,  particularly 
in  the  mesenteries.  According  to  Schumacher  (Arch.  f.  mikr.  Anat., 
1911,  vol.  77,  pp.  157-191)  the  lamellar  corpuscles  become  inflated  when 
the  blood-pressure  is  increased,  and  "their  structure  and  distribution, 
together  with  the  results  of  experiments,  indicate  that  they  are  regulators 
of  the  blood  pressure. " 


.    NERVOUS   TISSUE  ^3 

MOTOR  ENDINGS.  The  motor  nerve  endings  are  the  terminations  of 
efferent  nerves,  in  contact  with  smooth,  cardiac  or  striated  muscle  fibers. 
The  nerves  to  the  smooth  muscles  are  a  part  of  the  sympathetic  system. 
They  are  non-medullated  fibers  which  branch  repeatedly,  forming  plexuses. 
From  the  plexuses  very  slender  varicose  fibers  proceed  to  the  muscle  cells, 
in  contact  with  the  surface  of  which  they  end  in  one  or  two  terminal  or 
lateral  nodular  thickenings.  Probably  each  muscle  cell  receives  a  nerve 
termination.  Except  that  the  nerve  endings  in  heart  muscle  are  a  little 
larger,  often  provided  with  a  small 
cluster  of  terminal  nodules,  they  are 
like  those  of  smooth  muscle. 

Striated  muscles  are  innervated 
by  the  neuraxons  of  the  ventral  roots, 
which  grow  out  from  cell  bodies  re-  Pio  I58._MolOR  PLAIES. 

maining    within    the    Central    System.        A,   Surface  view,  from  a  guinea-pig;  B,  vertical 

section,  from  a  hedgehog.     (After  Bohm  and 

They  form  plexuses  of  medullated  SS^f^/li^mSd^l^ 
fibers  in  the  perimysium,  from  which  gj£;  *•  '•• tenninal  ramifications  of  the  nerve 
branching  medullated  fibers  extend 

into  the  fasciculi  (Fig.  157).  Each  muscle  fiber  receives  one  of  these 
branches,  or  sometimes  two  placed  near  together.  They  are  usually 
implanted  near  the  middle  of  the  muscle  fiber.  The  connective  tissue 
sheath  of  the  nerve  blends  with  the  perimysium,  and  the  neurolemma 
is  said  to  be  continuous  with  the  sarcolemma.  On  the  inner  side  of 
the  sarcolemma  the  myelin  sheath  ends  abruptly,  and  the  nerve  fiber 
ramifies  in  a  granular  mass  considered  to  be  modified  sarcoplasm,  which 
may  contain  muscle  nuclei.  This  entire  structure  appears  as  a  distinct 
elevated  area,  estimated  to  average  from  40  to  60  p  in  diameter;  it  has 
been  named  the  motor  plate.  A  surface  view  and  a  section  of  a  motor 
plate  are  shown  in  Fig.  158. 


VASCULAR  TISSUE. 

Vascular  tissue  includes  the  blood  vessels,  the  heart,  and  the  lymphatic 
vessels,  together  with  the  blood  and  the  lymph. 

BLOOD  VESSELS. 

GENERAL  FEATURES.  The  existence  of  blood  vessels  was  well  known 
to  the  ancient  anatomists,  and  a  distinction  was  sometimes  made  between 
pulsating  and  non-pulsating  vessels.  They  were  all  included  by  Aristotle 
under  the  term  <f>X&(/  (vein).  He  described  the  two  great  vessels  at  the 
back  of  the  thorax,  one  of  which  is  the  vena  cava;  the  other,  as  he  states, 
"by  some  is  termed  the  aorta,  from  the  fact  that  even  in  dead  bodies 


164  HISTOLOGY 

part  of  it  is  observed  to  be  full  of  air."  He  added  that  "  these  blood  vessels 
have  their  origins  in  the  heart,  for  in  whatever  direction  they  happen  to 
run,  they  traverse  the  other  viscera  without  in  any  way  losing  their  dis- 
tinctive characteristics  as  blood  vessels;  whereas  the  heart  is,  as  it  were, 
a  part  of  them"  (Historia  Animalium,  Book  3,  trans,  by  Thompson). 
Subsequently  the  term  artery  was  applied  to  the  aorta  and  its  branches, 
which  were  found  partly  empty  of  blood  after  death,  and  were  believed 
to  convey  air;  the  windpipe  was  called  the  arteria  as  per  a. 

Vesalius  described  an  artery  as  "a  vessel  similar  to  a  vein,  membranous,  round, 
and  hollow  like  a  pipe,  by  means  of  which  vital  spirit  and  warm  blood,  rushing  impetu- 
ously, are  distributed  throughout  the  entire  body;  by  the  aid  of  these,  and  thus 
through  the  motion  of  the  artery  itself  (which  is  by  dilatation  and  contraction)  the 
vital  spirit  and  the  natural  warmth  of  the  several  parts  are  renewed"  (De  corporis 
humani  fabrica,  1543,  4th  ed.,  1604).  Vesalius  described  the  arteries  and  veins  as 
composed  of  coats  (tunica)  in  which  he  found  loose  tissue  and  layers  of  fibers — 
circular,  oblique,  and  longitudinal. 

The  valves  of  the  veins,  consisting  of  thin  membranes  projecting  into  their  lumens, 
were  first  described  and  clearly  figured  by  Fabricius,  under  whom  Harvey  studied 
at  Padua  (De  venarum  ostiolis,  1603).  Fabricius  observed  that  the  ostiola  are 
found  chiefly  in  the  veins  of  the  limbs  and  are  "open  toward  the  roots  of  the  veins  but 
closed  below."  He  considered  that  "to  a  certain  extent  they  hold  back  the  blood, 
lest;  like  a  stream,  it  should  all  flow  together  either  at  the  feet,  or  in  the  hands  and 
fingers."  He  stated  that  the  veins  can  be  easily  dilated  and  distended,  since  they  are 
composed  of  a  simple  and  thin  membranous  substance;  and  concluded  that  the  veins 
have  valves  to  prevent  over-distention,  but  the  arteries,  because  of  the  thickness 
and  strength  of  their  walls,  do  not  require  them. 

In  demonstrating  the  circulation  of  the  blood  (in  1628)  Harvey  contributed 
little  to  the  knowledge  of  the  structure  of  the  vessels.  He  could  not  find  the  micro- 
scopic connections  between  the  arteries  and  veins,  but  they  were  discovered  not  many 
years  later  by  Malpighi  (De  pulmonibus,  Ep.  II,  1661).  In  the  membranous  lungs 
of  frogs  and  turtles,  Malpighi  found  a  rete  QI  network  of  vessels  connecting  the  artery 
and  vein,  so  that  the  blood  was  not  poured  out  into  spaces,  but  was  driven  through 
tubules.  He  concluded  that  if  in  one  case  the  ends  of  the  vessels  are  brought  together 
in  a  rete,  similar  conditions  exist  elsewhere,  and  he  observed  the  circulation  taking 
place  in  the  diaphanous  anastomosing  vessels  of  the  distended  bladder  of  frogs. 
Leeuwenhoek  (1698)  clearly  figured  the  minute  vessels  which  pass  from  the  arteries 
to  the  veins  in  the  caudal  fin  of  eels,  and  noted  that  the  line  of  separation  between  the 
artery  and  vein  is  arbitrary. 

The  vessels  which  connect  the  arteries  with  the  veins,  because  of  their 
hair-like  minuteness,  were  later  called  capillaries.  Physiologically  they 
form  the  most  important  part  of  the  vascular  system,  and  anatomically 
they  are  the  most  fundamental.  They  consist  merely  of  endothelial 
tubes.  All  larger  vessels,  not  only  the  arteries  and  veins,  but  also  the 
heart,  are  derived  from  endothelial  tubes  and  retain  their  endothelial  lining. 
The  endothelium,  however,  becomes  surrounded  by  layers  of  smooth 
muscle  fibers  and  connective  tissue,  which  form  the  substance  of  the 


BLOOD  VESSELS  165 

vessel  walls.  The  arteries  in  general  have  thicker  and  more  elastic  walls 
than  the  veins,  and  tend  to  remain  open  after  death;  the  thinner  walls 
of  the  veins  are  prone  to  collapse. 

DEVELOPMENT.  In  an  early  stage  the  blood  vessels  of  the  embryo 
form  a  network  in  the  splanchnopleure.  In  mammals,  as  in  the  chick 
(Figs.  27  and  28,  p.  40),  the  portion  of  the  net  nearest  the  median  line 
forms,  on  either  side  of  the  body,  a  longitudinal  vessel,  the  dorsal  aorta. 
The  part  of  the  net  folded  under  the  pharynx  constitutes  successively 
(beginning  posteriorly)  the  vitelline  veins,  the  heart,  and  the  ventral  aorta, 
and  the  latter  .are  continuous  in  front  of  the  pharynx  with  the  dorsal  aortae. 
The  heart  first  appears  as  two  dilated  vessels,  one  on  either  side,  which 
are  parts  of  the  general  network.  They  are  brought  together  in  the  median 
line  under  the  pharynx  and  fuse.  At 
first  the  heart  pulsates  irregularly, 
but  with  the  establishment  of  the 
circulation,  its  beats  become  rhyth- 
mical. The  blood  flows  from  the 
general  network  through  the  veins  to 
the  heart,  and  thence  through  the 
arteries  back  to  the  net.  All  the 
future  vessels  of  the  body  are  be- 
lieved to  be  offshoots  from  the  en- 

FIG.  159. 

dothelial  tubes  jUSt  described.       They       Blood   vessels  from  a  rabbit  embryo  of  13  days, 

.  developing   as  endothelial  sprouts  (en)    from 

grOW      OUt,     as     Shown     in     Fig.      I^Q,  pre-existing  vessels   (b.v.);    b.c.,    blood  cor- 

puscle within  a  vessel. 

through  the  mesenchyma  with  which 

they  often  appear  to  be  inseparably  connected.  The  sprouts  are  at 
first  solid,  but  soon  become  hollow  except  at  the  growing  tips.  They 
may  encounter  similar  offshoots  from  the  same  or  other  vessels  and 
fuse  with  them.  Through  the  anastomosis  of  such  sprouts  new  capillary 
nets  are  produced. 

The  formation  of  a  definite  system  of  arteries  and  veins  out  of  a  general 
network  may  be  partly  explained  on  mechanical  principles.  The  vascular 
outgrowths  must  take  certain  courses  marked  out  by  the  epithelial  struc- 
tures. Thus  in  early  stages  they  may  grow  between  the  somites,  but  not 
into  them,  producing  a  series  of  segmental  vessels;  they  pass  around  the 
front  of  the  fore-gut  and  up  and  down  between  its  lateral  outpocketings, 
so  that  the  regular  system  of  aortic  arches  appears  to  depend  upon  these 
epithelial  obstructions;  and  they  are  guided  along  the  under  surface  of  the 
developing  brain  in  a  very  characteristic  manner.  Epithelial  obstructions 
therefore  determine  the  position  of  the  capillary  plexuses.  In  each  plexus 
the  favorable  channels  enlarge  and  become  the  main  arteries  and  veins, 
sending  forth  new  branches  and  acquiring  thick  walls;  whereas  the 
vessels  in  which  the  current  is  slow  remain  small  or  disappear. 


1 66  HISTOLOGY 

These  factors  are  further  considered  by  Thoma  (Histomechanik  des 
Gefasssystems,  1893). 

The  way  in  which  main  trunks  develop  from  indifferent  networks  has  been  described 
by  Evans  on  the  basis  of  extraordinarily  perfect  injections;  thin  fluid  introduced  into 
the  vessels  of  a  living  chick  embryo  is  distributed  throughout  the  vascular  system 
by  the  action  of  the  heart  (Anat.  Rec.,  1909,  vol;  3,  pp.  498-518).  Obviously  how- 
ever if  vessels  are  arising  as  mesenchymal  spaces  which  subsequently  become  joined  to 
the  vascular  system,  they  would  not  be  revealed  by  this  method.  The  existence  of 
detached  spaces  in  rabbit  embryos  has  been  denied  by  Bremer,  after  making  very 
careful  graphic  reconstructions  of  all  the  vessels  in  the  anterior  end  of  the  specimens 
studied.  He  finds  that  a  network  consisting  largely  of  solid  strands  precedes  the 
network  of  open  tubes  (Amer.  Journ.  Anat.,  1912,  vol.  13,  pp.  111-128).  Schafer, 
however,  describes  the  formation  of  vessels  by  the  vacuolization  of  connective 
tissue  cells,  which  then  become  connected  with  processes  from  pre-existing  capillaries, 
and  so  added  to  the  endothelium.  He  states  that  "a  more  or  less  extensive  capillary 
network  is  often  formed  long  before  the  connection  with  the  rest  of  the  vascular 
system  is  established"  (Text-book  of  Micr.  Anat.,  1912).  His  observations  were 
made  upon  subcutaneous  tissue  of  the  new-born  rat.  Similar  appearances  in  the 
subcutaneous  tissue  of  human  embryos  may  be  interpreted  quite  differently,  and 
before  it  can  be  accepted  that  the  cells  containing  red  corpuscles  are  detached  from 
the  vascular  system,  careful  reconstructions  are  required. 

The  formation  of  anomalous  vessels  readily  takes  place  by  the  persistence  and 
enlargement  of  channels  usually  unfavorable.  This  is  discussed  by  S.  R.  Williams  in 
explaining  the  condition  observed  in  an  adult  salamander,  in  which  one  of  the  long  and 
slender  lungs  received  its  artery  at  the  anterior  end  and  the  other  at  the  posterior 
end  (Anat.  Rec.,  1909,  vol.  3,  pp.  409-414).  Innumerable  forms  of  human  vascular 
anomalies  may  thus  be  explained  embryologically;  some  of  them  represent  persistent 
vessels  which  are  normally  important  at  a  certain  stage  of  development,  and  others 
represent  connections  which  are  as  abnormal  in  the  embryo  as  in  the  adult  (cf .  Lewis, 
Amer.  Journ.  Anat.,  1909,  vol.  9,  pp.  33-42). 

A  very  characteristic  form  of  circulation  occurs  in  certain  organs,  in 
which  the  endothelium  of  the  vessel  walls  is  closely  applied  to  the  epithe- 
lium of  the  secreting  tubules,  or  other  parenchymal  structure  (Fig.  160). 
The  walls  of  the  vessels  are  as  thin  as  those  of  capillaries,  but  their  di- 
ameter is  much  greater,  so  that  they  have  been  described  as  lacunar  ves- 
sels'or  "sinusoids,"  the  term  sinus  being  generally  applied  to  the  large 
thin- walled  veins  in  the  dura  mater  about  the  brain  (Minot,  Proc.  Boston 
Soc.  Nat.  Hist.,  1900,  vol.  29,  p.  185-215).  Apparently  the  close  ap- 
position of  the  endothelium,  on  all  sides,  to  the  cells  of  the  parenchyma 
is  the  most  essential  characteristic  of  these  vessels  and  must  be  of  con- 
siderable physiological  significance.  There  are  few  or  no  connective 
tissue  cells  between  the  thin  lining  of  the  vessel  and  the  epithelial  tissue 
which  it  nourishes.  Capillaries,  on  the  contrary,  are  imbedded  in  con- 
nective tissue,  even  though  occasionally  they  approach  close  to  an  epithe- 
lium, sometimes  appearing  to  enter  it.  In  the  lungs  the  capillaries  are 
compressed  between  epithelial  plates,  but  they  do  not  resemble  the  ves- 
sels shown  in  Fig.  160. 


BLOOD  VESSELS 


I67 


Where  sinusoids  are  most  highly  developed,  as  in  the  liver  and  Wolffian  body  of 
embryos,  they  possess  another  very  significant  characteristic.  They  are  not  con- 
nections between  an  artery  and  a  vein,  like  the  capillaries,  but  are  subdivisions  of 
veins.  Thus  in  the  liver,  as  shown  in  the  diagram,  Fig.  161,  the  portal  vein  enters  the 
organ  and  is  subdivided  by  cords  of  hepatic  cells  into  sinusoids,  such  as  are  shown  in 
section  in  Fig.  160.  These  reunite  to  empty  into  the  vena  cava  inferior.  The  sinusoids 


x300 

FIG.  160. — SINUSOIDS  (Si)  IN  THE  LIVER  OF  A  CHICK  EMBRYO  OF  ELEVEN  DAYS. 
h.c.,  Cords  and  tubules  of  hepatic  cells. 


(Minot.) 


of  the  liver  have  therefore  been  described  as  formed  by  the  intercrescence  of  vascular 
endothelium  and  hepatic  parenchyma.  This  arrangement  of  veins  constitutes  the 
hepatic  portal  circulation,  taking  its  name  from  the  entering  vessel.  The  same  type  of 
venous  circulation  occurs  in  the  Wolman  bodies,  where  it  constitutes  the  "renal  portal 
circulation,"  although  it  has  no  connection  with  the  portal  vein.  It  is  probable  that 
this  form  of  circulation,  which  is  generally  lacunar  or  sinusoidal,  represents  a  primitive 


VC.L 


V  Ar 


PIG.  161. — DIAGRAM  SHOWING  ON  THE  LEFT  THE  LIVER  AND  ITS  SINUSOIDS;  ON  THE  RIGHT  THE  PANCREAS 

AND  ITS  CAPILLARIES. 

The  connective  tissue  is  represented  by  dots.     Ar.,  Artery;  Int.,  intestine;  V.,  vein;  V.  C.  I.,  vena  cava 

inferior;  V.  P.,  portal  vein. 

type  of  vascularization,  since  a  single  vessel  passing  by  or  through  an  organ  provides  it 
with  both  afferent  and  efferent  vessels.  The  arterio-venous  circulation  requires  the 
presence  of  two  vessels  with  currents  flowing  in  opposite  directions.  There  are  indica- 
tions that  various  organs  in  the  human  embryo  have  a  transient  "portal  circulation" 
before  the  arteries  connect  with  the  network  and  become  the  main  afferent  channels. 

CAPILLARIES.     The  capillaries  are  endothelial  tubes  of  varying  di- 
ameter, the  smallest  being  so  narrow  that  the  blood  corpuscles  must  pass 


I 68  HISTOLOGY 

through  them  in  single  file.  Their  walls  are  composed  of  elongated,  very 
flat  cells,  with  irregularly  wavy  polygonal  outlines  which  are  clearly 
demonstrated  in  silver  nitrate  preparations  (Fig.  162).  Between  the  cells, 
the  red  and  white  corpuscles  frequently  make  their  way  out  of  the  vessel. 
There  are  no  pre-formed  openings  for  this  purpose,  and  the  endothelial 
cells  come  together  after  the  corpuscles  have  passed  out.  Certain  en- 
dothelial cells  are  phagocytic,  devouring  objects  which  float  in  the  blood; 
some  of  them  may  become  detached  and  enter  the  circulation.  More- 
over endothelial  cells  are  contractile,  and  may  be  stimulated  to  activity 

by  the  sympathetic  fibers  in  the  delicate 
perivascular  plexus  which  is  shown  in 
methylene  blue  preparations.  Some  of  the 
fibers  end  in  contact  with  the  cells  and  pre- 
sumably control  the  caliber  of  the  vessel; 
other  fibers  may  be  afferent  and  receive  a 
stimulus  when  the  vessel  expands  and 
stretches  the  plexus.  The  bulging  of  endo- 

PREPARATION.     (After  Koelliker.)         ,-,.•,  i    •    •     ,         i       i  f  i        <• 

thehal  nuclei  into  the  lumen  of  vessels,  fre- 
quently seen  in  preserved  specimens,  is  probably  due  to  post-mortem 
contraction;  in  life  the  lining  is  presumably  smooth. 

Although  capillaries  vary  in  diameter  (4.5-12  ju)>  those  in  a  given 
territory  are  quite  uniform,  both  as  to  caliber  of  individual  vessels  and 
the  size  and  pattern  of  the  meshes  in  the  network.  The  closest  meshes 
and  largest  capillaries  occur  in  secretory  organs  and  in  the  lungs,  which 
are  therefore  abundantly  supplied  with  blood.  The  muscles  are  well 
supplied  by  slender  capillaries  in  a  rectangular  meshwork.  Serous  mem- 
branes and  dense  connective  tissue  have  a  scanty  blood  supply,  from  nar- 
row capillaries  in  a  coarse  net. 

ARTERIES.  The  walls  of  the  arteries  are  composed  of  three  layers — 
the  tunica  intima,  tunica  media,  and  tunica  externa,  respectively.  The 
intima  includes  the  endothelium  and  generally  an  underlying  elastic 
membrane,  separated  from  the  endothelium  by  a  small  amount  of  fibrous 
tissue.  The  media  is  primarily  a  layer  of  circular  smooth  muscle  fibers; 
and  the  externa  (formerly  called  the  tunica  adventitia)  consists  chiefly 
of  connective  tissue.  The  thickness  of  all  these  layers  is  greatest  toward 
the  heart.  They  become  thinner  at  the  places  where  the  arteries  branch, 
and  in  the  pre-capillary  vessels  nothing  remains  but  the  endothelium. 

The  small  terminal  arteries  are  called  arterioles.  They  are  endothelial 
tubes  encircled  by  scattered  smooth  muscle  fibers.  In  Fig.  163,  C,  the 
oval  nuclei  of  the  endothelium  are  seen  to  be  elongated  parallel  with  the 
course  of  the  vessel.  As  is  usually  the  case,  the  walls  of  the  endothelial 
cells  are  not  visible.  The  rod-shaped  nuclei  of  the  muscle  fibers  are  at 
right  angles  with  the  axis  of  the  vessel.  In  the  somewhat  larger  artery, 


ARTERIES 


169 


B,  the  muscle  fibers  form  a  single  but  continuous  layer,  the  media,  out- 
side of  which  the  connective  tissue  is  compressed  to  make  the  externa. 
Its  fibers  tend  to  be  parallel  with  the  vessel.  The  walls  of  such  an  artery 
are  so  thick  that  it  is  possible  to  focus  on  the  layers  separately;  thus  in  A, 
the  endothelium,  which  with  a.  delicate  elastic  membrane  beneath  it  con- 
stitutes the  intima,  is  not  seen,  being  out  of  focus.  The  nuclei  of  the 


FIG.  163. — FRAGMENTS  OF  HUMAN  ARTERIOLES.     X  240. 

i^Nuclei  of  endothelial  cells;  m,  nuclei  of  circular  muscle  fibers;  a,  nuclei  of  connective  tissue. 
In  A,  since  the  endothelium  is  out  of  focus,  its  nuclei  are  not  seen. 

media  and  externa  are  evident.     A  cross  section  of  such  a  vessel  is  seen 
in  Fig.  177. 

The  larger  arteries  are  lined  with  endothelium  similar  to  that  of  the 
capillaries,  as  shown  in  silver  nitrate  preparations  (Fig.  164).  This  endo- 
thelium rests  on  a  layer  of  connective  tissue  containing  flattened  cells 
and  a  network  of  fine  elastic  fibers.  The  meshes  of  the  fibrous  and  elastic 


Endothelial  cell. 


Indentations  made  by  smooth  muscle  fibers. 


FIG.  164. — ENDOTHELIUM  OF  A  MESENTERIC  ARTERY  OF  A  RABBIT.     SURFACE  VIEW.     X  250. 

tissue  are  elongated  lengthwise  of  the  vessel,  and  on  surface  view  they 
present  a  longitudinally  striped  appearance.  In  addition  to  this  subendo- 
thelial  tissue  and  the  endothelium,  the  intima  includes  the  inner  elastic 
membrane  (Fig.  165).  This  is  usually  a  conspicuous  layer  thrown  into 
wavy  folds  by  the  post-mortem  contraction  of  the  vessel.  It  is  easily 
seen  with  ordinary  stains,  appearing  as  a  refractive  layer,  and  is  deeply 


170 


HISTOLOGY 


colored  by  resorcin-fuchsin  and  other  elastic  tissue  stains  (upper  segment 
in  Fig.  165).  In  smaller  arteries  the  endothelium  appears  to  rest  directly 
upon  the  elastic  network  which  replaces  this  membrane;  and  in  such 
large  ones  as  the  external  iliacs,  the  principal  branches  of  the  abdominal 
aorta,  and  the  uterine  arteries  in  young  persons,  the  subendothelial  tissue 
is  said  to  be  lacking.  The  inner  elastic  membrane  is  not  a  continuous 
sheet  of  tissue,  since  it  is  perforated  by  elongated  apertures;  it  forms  a 


Artery. 


S'SfSH^vlS 

lltpfif' 

$to*^fp  -•••" 


f  Endothelium. 
Intima  ]  Inner  elastic 
(  membrane. 


f  Muscle  fibers. 
Media  j 

I  Conn,  tissue. 


Externa 


This  portion  is 
shown  enlarged 
on  the  left. 


e          f  g 

FIG.  165. — A  SECTION  THROUGH  A  HUMAN  ULNAR  ARTERY  AND  VEIN,  SHOWING  THE  WALL  OF  THE  ARTERY 

ON  THE  LEFT  AND  OF  THE  VEIN  ON  THE  RIGHT.     THE  UPPER  PART  OF  THE  FIGURE  (a-d)  is  FROM  A 

SECTION  OF  THE  SAME  VESSELS  STAINED  WITH  RESORCIN-FUCHSIN,  AN  ELASTIC  TISSUE  STAIN.     X  550 . 

a»  Circular,  and  b,  radial  elastic  fibers  of  the  media  of  the  artery;  c,  external  elastic  membrane;  d,  elastic 

fibers  in  the  media  of  the  vein;  e,  circular,  and  g,  longitudinal  muscle  fibers  of  the  media;  f,  endothelium. 

fenestrated  membrane  and  the  development  of  such  membranes  from  elastic 
networks  has  already  been  described  (cf.  Fig.  54,  p.  67).  The  membrane 
is  particularly  thick  in  the  larger  arteries  of  the  brain,  and  it  is  sometimes 
double. 

The  media,  which  consists  of  but  a  single  layer  of  circular  muscle 
fibers  in  the  pre-capillary  vessels,  becomes  many-layered  in  larger  arteries. 
Generally  the  fibers  are  all  circular  or  perhaps  oblique,  but  in  the  loose 
musculature  of  the  umbilical  arteries,  longitudinal  fibers  are  numerous. 
Longitudinal  fibers  are  said  to  occur  in  certain  other  vessels  near  the  intima, 
being  especially  well  developed  in  the  subclavian  artery.  The  post-mor- 
tem contraction  of  the  circular  fibers,  which  throws  the  intima  into  folds, 


ARTERIES  171 

causes  a  spiral  crumpling  of  certain  muscle  nuclei,  the  significance  of 
which  has  already  been  discussed  (Fig.  106,  p.  117).  Between  the  muscle 
fibers  there  are  circular  elastic  fibers,  or  plates  in  the  larger  vessels,  which 
are  thrown  into  wavy  folds.  Radial  fibers,  which  connect  these  in  a 
general  network,  are  slender  and  require  special  staining.  White  fibers 
are  present,  apparently  formed  in  considerable  part  by  the  muscle  fibers 
which  they  bind  together.  The  proportion  between  the  muscular  and 
elastic  tissue  in  the  media  varies  in  different  arteries.  In  the  smaller 
vessels,  the  muscular  tissue  predominates,  and  this  is  true  also  of  the 
cceliac,  femoral  and  radial  arteries.  But  in  the  common  iliac,  axillary 
and  carotid  arteries  the  elastic  tissue  prevails,  and  in  this  respect  they 
resemble  the  largest  arteries — the  aorta  and  pulmonary  artery. 

The  externa  is  a  connective  tissue  layer  which  sometimes  contains 
scattered  bundles  of  longitudinal  muscle  fibers.  It  has  many  longitudinal 
elastic  fibers,  which  are  particularly  numerous  toward  the  media,  where 
they  are  often  grouped  as  the  external  elastic  membrane  (Fig.  165).  This 
is  not  a  fenestrated  membrane,  but  is  merely  a  dense  zone  of  longitudinal 
fibers.  It  is  said  to  be  well  developed  in  the  carotid,  brachial,  femoral, 
cceliac  and  mesenteric  arteries,  and  to  be  absent  from  the  basilar  and 
other  cerebral  arteries. 

Nerves  and  vessels  ramify  in  the  externa.  The  walls  of  the  larger 
arteries  are  supplied  with  small  blood  vessels,  the  vasa  wsorum,  derived 
from  adjacent  arteries.  These  are  distributed  chiefly  to  the  externa; 
they  may  penetrate  the  outer  part  of  the  media  but  do  not  reach  the  in- 
tima.  Lymphatic  vessels  form  perivascular  plexuses,  and  send  branches 
into  the  externa.  The  nerves  are  medullated  and  non-medullated.  They 
include  vasomotor  fibers  which  innervate  the  smooth  muscle  cells,  and 
sensory  or  afferent  nerves  which  have  terminal  arborizations  in  the  intima 
and  in  the  externa.  Other  nerve  fibers  end  in  lamellar  corpuscles  in  the 
externa  of  the  aorta  and  other  large  vessels. 

Ganglia  are  not  seen  in  the  walls  of  the  vessels,  and  the  sympathetic 
fibers  to  the  muscles  therefore  travel  considerable  distances  to  their  ter- 
minations. In  this  respect  the  nerves  to  the  smooth  muscles  of  the  ves- 
sels differ  from  those  to  the  musculature  of  the  digestive  tube. 

In  the  largest  arteries  (the  aorta  and  pulmonary  arteries)  the  intima 
is  very  broad  (Fig.  166),  and  it  increases  in  thickness  with  age.  Its  en- 
dothelial  cells  are  less  elongated  than  those  of  smaller  arteries.  They 
rest  on  a  fibrous  subendothelial  tissue,  containing  flattened  stellate  or 
rounded  cells,  and  networks  of  elastic  tissue.  The  elastic  fibers  are  thicker 
toward  the  media,  finally  producing  a  fenestrated  membrane  which  corre- 
sponds with  the  inner  elastic  membrane  of  smaller  vessels,  but  which  is 
scarcely  thicker  than  adjacent  elastic  lamellae.  The  broad  media  consists 
of  elastic  membranes  and  muscle  fibers,  but  the  elastic  tissue  greatly 


172 


HISTOLOGY 


predominates.  On  section  the  wall  of  the  fresh  aorta  consequently 
appears  yellow,  and  not  reddish  like  the  more  muscular  walls  of  smaller 
arteries.  The  elastic  tissue  is  arranged  in  a  succession  of  circular  fenes- 
trated  membranes  connected  with  one  another  by  oblique  fibers.  Be- 
tween them  are  the  muscle  cells.  According  to  Koelliker,  in  the  inner 
layers  of  the  media,  the  muscle  cells  form  an  anastomosing  syncytium 

of  short,  broad  and  flattened  ele- 
ments, somewhat  resembling  car- 
diac muscle  (Fig.  167),  but  in  the 
outer  layers  the  fibers  are  of  the 
ordinary  type.  The  externa  con- 
tains no  outer  elastic  layer  and  is 
relatively  thin;  its  inner  elastic 
portion  may  have  been  taken  over 
into  the  media. 

VEINS.  Since  the  artery  to 
any  structure  and  the  returning 
vein  are  often  side  by  side,  they 
are  frequently  included  in  a  single 
section  and  may  readily  be  com- 
pared. In  embryos  the  veins  are 
of  much  larger  diameter  than  the 
corresponding  arteries,  and  they 
have  thinner  walls.  Although 


Vasa  vasorum. 


FIG.  166. — FROM  A  TRANSVERSE  SECTION  OF  THE 
HUMAN  THORACIC  AORTA,  STAINED  WITH  RE- 
SORCIN-FUCHSIN.  X  8O. 

a,  Endoth'elium ;  b,  subendothelial  fibrous  tissue; 
c,  d,  elastic  membranes  of  the  media. 


FIG.  167. — BRANCHED  SMOOTH  MUSCLE 
CELLS  FROM  THE  THORACIC  AORTA  OF 
A  CHILD  AT  BIRTH  (a)  AND  AT  FOUR 
YEARS  (b).  (After  Koelliker.) 


the  difference  in  diameter  is  less  marked  in  the  adult,  it  generally  remains 
a  distinctive  feature  (Fig.  177,  p.  186),  and  the  difference  in  the  thickness 
of  the  walls  becomes  accentuated  (Fig.  165).  In  comparing  the  diameters 
of  the  ulnar  vein  and  artery  in  Fig.  165,  it  should  be  remembered  that  the 
ulnar  artery  is  usually  accompanied  by  two  returning  veins,  only  one  of 
which  is  shown  in  the  figure.  Because  of  their  thinner  walls,  which  con- 
tain relatively  little  elastic  tissue,  the  veins  are  generally  partly  collapsed; 
the  lumen  is  therefore  irregular,  whereas  that  of  the  arteries  tends  to  be 


VEINS 


173 


This  portion  is  enlarged  below 

Endothelium. 
\ 


^p||iii 


"^•""^i 

"41 

*>""•» 

**£•** 


round   (Fig.   165).     Small  veins  full  of  blood  may  be  round,  however, 
and  the  arteries  are  sometimes  irregularly  contracted. 

The  walls  of  the  veins,  like  those  of  arteries,  are  composed  of  three 
layers,  the  intima,  media,  and  externa.  The  intima  includes  the  primary 
endothelium,  which  is  composed 
of  polygonal  cells,  generally  shorter 
and  broader  than  those  of  arteries. 
The  endothelium  rests  on  a  thin 
layer  of  subendothelial  fibrous 
tissue.  The  inner  elastic  mem- 
brane of  arteries  is  represented  in 
the  smaller  veins  by  a  thin  homo- 
geneous membrane,  but  in  larger 
veins  it  is  replaced  by  a  network 
of  elastic  fibers  (Fig.  165).  In 
addition  to  these  structures  the 
intima  of  certain  veins  contains 
scattered  oblique  and  longitudinal 
muscle  fibers;  they  are  said  to 
occur  in  the  iliac,  femoral,  saphen- 
ous  and  intestinal  veins,  the  intra- 
muscular part  of  the  uterine  veins, 
and  especially  in  the  dorsal  vein  of 
the  penis  near  the  suspensory  liga- 
ment. 

The  media  shows  great  varia- 
tions. It  is  generally  a  thin  layer 
consisting  of  circular  muscle  fibers, 
elastic  networks  and  relatively 
abundant  connective  tissue,  and  is 
best  developed  in  the  veins  of  the 
lower  extremity  (especially  the 
popliteal).  In  those  of  the  upper 
extremity  it  is  not  so  well  marked, 
and  it  is  still  thinner  in  the  larger  L 1 

Veins  Of  the  abdominal  Cavity;    it    FlG.  I68.— FROM  A  CROSS  SECTION  OF  A  HUMAN  SUPRA 

is  reduced  to  fibrous  tissue  and  is 
essentially  absent  from  the  vena 
cava  superior,  the  veins  of  the 
retina,  of  the  pia  and  dura  mater,  and  of  the  bones. 

The  externa  is  the  most  highly  developed  layer  of  the  veins.  It  con- 
sists of  interwoven  bundles  of  connective  tissue,  elastic  fibers,  and  longi- 
tudinal bundles  of  smooth  muscles  which  are  more  abundant  than  in  the 


sue;  c,  d,  longitudinal  muscle  fibers  of  the  externa; 
e>  connective  tissue;  f,  small  vein;  g,  fat  cell. 


174  HISTOLOGY 

arteries.  In  certain  veins  (e.g.,  the  main  trunk  of  the  portal,  the  renal 
and  suprarenal  veins)  the  longitudinal  muscle  forms  an  almost  complete 
layer  of  considerable  thickness  (Fig.  168). 

The  valves  of  veins  are  paired  folds  of  the  intima,  each  shaped  like 
half  of  a  cup  attached  to  the  wall  of  the  vein  so  that  its  convex  surface 
is  toward  the  lumen.  In  longitudinal  section  they  appear  like  the  valves 
of  the  lymphatic  vessel  shown  in  Fig.  179.  The  valves  are  generally 
found  distal  to  the  point  where  a  branch  empties  into  the  vein,  and  they 
prevent  its  blood  from  flowing  away  from  the  heart.  They  are  most 
numerous  in  the  veins  of  the  extremities,  but  appear  also  in  the  inter- 
costal, azygos,  spermatic,  and  certain  other  veins;  none  are  found  in  the 
vertical  trunks  of  the  superior  and  inferior  venae  cavae.  They  counter- 
act the  effects  of  gravity  upon  the  blood,  and  it  has  been  suggested  that 
their  arrangement  in  man  corresponds  rather  to  a  quadrupedal  attitude 
than  to  an  upright  position.  The  endothelial  cells  on  the  surface  of  the 
valve  toward  the  lumen  of  the  vein  are  elongated  parallel  with  the  current, 
and  beneath  them  there  is  a  thick  network  of  elastic  tissue.  On  the  side 
of  the  valve  toward  the  wall  of  the  vein,  the  long  axis  of  the  cells  is  trans- 
verse, and  there  the  cells  rest  upon  fibrous  connective  tissue. 

THE  HEART. 

DEVELOPMENT.  The  heart  has  already  been  described  as  a  median 
longitudinal  vessel  situated  beneath  the  pharynx,  formed  posteriorly 
by  the  union  of  the  vitelline  veins,  and  terminating  anteriorly  in  the 
two  ventral  aortse  (Figs.  27  and  28,  p.  40).  This  endothelial  tube  is 
surrounded  by  the  mesothelium  of  the  body  cavity,  except  along  its 
dorsal  border,  where  it  is  attached,  as  it  were  by  a  short  mesentery,  to 
the  under  side  of  the  fore-gut.  If  the  embryo  is  placed  in  an  upright 
position,  corresponding  with  that  of  the  adult,  the  relations  of  the  heart 
to  the  body  cavity  will  be  as  shown  in  the  diagram,  Fig.  169,  A.  The 
posterior  part  of  the  body  cavity,  which  becomes  the  peritoneal  cavity, 
extends  forward  on  either  side  and  comes  together  across  the  median 
line  beneath  the  heart,  thus  forming  the  pericardial  cavity.  As  the  heart 
develops  it  becomes  bent  upon  itself  as  shown  in  Fig.  169,  B;  and  below 
it,  a  shelf  of  tissue  forms  across  the  body,  representing  the  future  dia- 
phragm. Dorsal  to  the  diaphragm,  the  pericardial  cavity  still  communi- 
cates with  the  peritoneal  cavity,  on  either  side  of  the  body.  In  the 
region  of  this  communication  the  lungs  later  develop,  and  partitions 
separate  the  part  of  the  body  cavity  around  them,  namely  the  pleural 
cavity,  from  the  pericardial  and  peritoneal  cavities  respectively.  These 
partitions  are  the  pleuro-pericardial  membrane  and  the  membranous 
part  of  the  diaphragm  (Fig.  169,  C).  Meanwhile  the  mesentery  of 


HEART 


175 


the  heart  has  become  thin  and  has  ruptured  in  the  hollow  of  the  U- 
shaped  bend,  forming  the  sinus  transversus  pericardii,  which  persists 
throughout  life  as  a  small  but  very  definite  structure. 

While  the  heart  is  still  a  simple  tube  consisting  of  endothelium  inter- 
nally and  mesothelium  externally,  with  a  space  between  them  bridged 
by  protoplasmic  strands,  it  beats  regularly,  although  possessing  neither 
nerves  nor  muscles.  Without  causing  any  interruption  of  the  circulation 
the  simple  tube  becomes  divided  into  four  chambers,  namely  the  right 
and  left  atria  (or  auricles1)  and  the  right  and  left  ventricles.  The  process 
of  subdivision  may  be  outlined  as  follows: 

When  the  tube  becomes  bent  into  a  U,  the  venous  end  of  the  heart 
is  carried  anteriorly,  dorsal  to  the  aortic  end,  as  shown  in  Fig.  170,  A-C. 


HV. 


A  B  C 

FIG.  169. — DIAGRAMS  ILLUSTRATING  THE  FORMATION  OF  THE  PERICARDIAL  CAVITY. 

A.,  Aortic  end  of  heart;  B.  W.,  body  wall;  D.,  diaphragm;  Ht.,  heart;  Li.,  liver;  Lu.,  lung;  P.  C.,  pericardial 
cavity;  Per.,  peritoneal  cavity;  PL,  pleural  cavity;  S.p-p.,  pleuro-pericard^l  septum,  S.  tr.  p.,  sinus 
transversus  pericardii;  V.,  venous  end  of  the  heart. 

At  the  same  time  the  ventral  or  aortic  limb  of  the  U  is  carried  to  the  right 
of  the  median  plane  (C) .  The  dorsal  limb  is  divided  into  two  parts  by  an 
encircling  transverse  constriction,  the  coronary  sulcus  (s.c.).  Its  thick- 
walled  portion,  ventral  to  the  sulcus,  forms  the  ventricles;  the  thin-walled 
dorsal  portion  becomes  the  atria.  In  the  human  embryo  of  three  weeks 
(C)  the  atria  are  represented  by  a  single  cavity  subdivided  into  right  and 
left  parts  only  by  an  external  depression  in  the  median  plane.  The  right 
portion  receives  all  the  veins  which  enter  the  heart  (the  vitelline  veins  and 
their  tributaries)  and  is  much  larger  than  the  left  portion.  The  cavities  of 
the  atria  not  only  freely  communicate  with  each  other  but  they  have  a 
common  outlet  into  the  undivided  ventricle.  From  the  ventricle  the 
blood  flows  out  of  the  heart  through  the  aortic  limb.  In  a  complex  manner, 
described  in  text-books  of  embryology,  a  median  septum  develops, 
dividing  the  heart  into  right  and  left  halves. 

In  the  heart  of  a  i2-mm.  pig  embryo  this  septum  has  already  formed 

1  According  to  the  anatomical  nomenclature  adopted  at  Basle,  the  term  auricle  (diminutive 
of  auris,  ear)  is  restricted  to  what  was  formerly  called  the  auricular  -appendix,  and  the  term 
atrium  (chamber)  is  used  for  the  cavity  as  a  whole. 


i76 


HISTOLOGY 


(Fig.  170,  D)  and  has  been  exposed  by  cutting  away  most  of  the  left 
atrium  and  left  ventricle.  The  septum  between  the  atria  becomes  per- 
forated as  it  develops,  so  that  in  embryonic  life  the  atria  always  commu- 
nicate. The  perforation  in  the  septum  is  the  foramen  ovale. 

Encircling  the  orifice  which  connects  each  atrium  with  the  correspond- 
ing ventricle,  there  is  a  ring  of  mesenchyma  which  in  the  adult  becomes 
dense  fibrous  tissue — the  annulus  fibrosus.  Extending  from  this  ring 
into  the  left  ventricle  there  are  two  flaps  of  tissue  partly  detached  from 
the  ventricular  walls.  They  constitute  the  bicuspid  valve  (or  mitral  valve). 
Toward  the  apex  of  the  heart  each  flap  passes  into  strands  of  tissue  at- 
tached to  the  walls  of  the  ventricle.  These  strands  become  the  chorda  ten- 


E F 

Fid.  170. — EMBRYONIC  HEARTS. 

A  and  B,  From  rabbitsonine  days  after  coitus;  C,  from  a  human  embryo  of  three  (?)  weeks;  D  and  E,  from  a 
12-mm.  pig  (D  sectioned  on  the  left  of  the  median  septum,  and  E  on  the  right  of  it);  F,  from  a  13.6- 
mm.  human  embryo,  sectioned  like  E.  The  hearts  are  all  in  corresponding  positions  with  the  left 
side  toward  the  observer,  the  anterior  end  toward  the  top  of  the  page,  the  dorsal  side  to  the  right. 
ao.,  Aorta;  c.  s.,  coronary  sinus;  f.  o.,  foramen  ovale;  i.  f.,  interventricular  foramen;  1.  a.,  left  atrium; 
p.  a.,  pulmonary  artery;  p.  v.,  pulmonary  vein;  r.  a.,  right  atrium;  s.,  septum  membranaceum  separating 
the  root  of  the  aorta  from  the  right  ventricle;  s.  c.,  coronary  sulcus;  v.,  ventricle;  v.  b.,  bicuspid 
valve;  v.  t.,  tricuspid  valve;  v.  v.»  vitelline  vein;  v.  v.  s.,  valves  of  the  venous  sinus. 

dinea  of  the  adult,  and  the  muscular  elevations  into  which  they  are  inserted 
are  the  papillary  muscles  (musculi  papillares).  The  differentiation  of 
these  structures  has  not  taken  place  in  the  stage  shown  in  Fig.  170. 

In  the  i2-mm.  pig  (Fig.  170,  D)  the  median  septum  which  has  grown 
up  from  the  apex  of  the  heart,  so  as  to  separate  the  right  and  left  ventricles 
from  each  other,  is  not  complete.  The  ventricles  still  communicate 
through  the  interventricular  foramen,  and  through  this  aperture  the  blood 
passes  from  the  left  side  of  the  heart  to  enter  the  root  of  the  aorta.  The 
root  of  the  aorta  is  shown  in  E,  a  section  of  the  same  heart  made  on  the 
right  of  the  median  septum.  The  pulmonary  artery  and  the  part  of  the 
aorta  near  the  heart  develop  first  as  a  single  vessel;  they  become  separated 
from  one  another  by  the  formation  of  a  partition.  As  long  as  the  dividing 


HEART 


177 


wall  is  incomplete,  the  blood  from  either  ventricle  may  pass  out  through 
either  artery  as  shown  in  E.  In  the  more  advanced  human  embryo,  F, 
the  partition  between  the4  aorta  and  pulmonary  artery  has  extended  so 
that  it  joins  the  interventricular  septum,  and  causes  the  interventricular 
foramen  to  open  into  the  root  of  the  .aorta  only  (s).  This  portion  of  the 
interventricular  wall  which  is  the  last  to  form,  is  translucent  in  the  adult, 
and  is  known  as  the  septum  membranaceum. 

As  previously  noted  all  the  veins  come  together  to  enter  the  right 
atrium.  The  original  vitelline  veins  are  no  longer  directly  connected 
with  the  heart,  and  their  persistent  cardiac  outlet  becomes  the  terminal 
part  of  several  large  branches.  These  are  the  superior  vena  cava  from 
the  head  and  arms,  the  inferior  vena  cava  from  the  trunk  and  legs  (receiv- 
ing as  branches  the  hepatic  vein  draining  the  portal  system  from  the  in- 
testine, and  the  umbilical  vein  from  the  placenta) ;  and  the  coronary  sinus 
which,  as  it  passes  across  the  heart  in  the  coronary  sulcus,  receives 
branches  from  the  wall  of  the  heart.  All  these  veins  come  together  in  a 
cavity,  ill  denned  in  mammals,  known  as  the  sinus  venosus,  and  this  sinus 
empties  into  the  right  atrium  through  an  orifice  guarded  by  a  valve  with 
right  and  left  flaps.  With  further  growth  the  sinus  venosus  becomes  a 
part  of  the  atrium,  and  the  superior  and  inferior  venae  cavse  and  coronary 
sinus  open  separately,  guarded  by  imperfect  valves  derived  from  the 
valves  of  the  sinus  venosus.  The  left  flap  of  this  valve  is  said  to  assist 
in  closing  the  foramen  ovale;  the  right  flap  becomes  subdivided  into  the 
rudimentary  valve  of  the  vena  cava  inferior  (Eustachian  valve)  and  the 
valve  of  the  coronary  sinus  (Thebesian  valve).  The  degeneration  of  the 
valve  of  the  venous  sinus  seems  to  take  place  after  the  bicuspid  and 
tricuspid  valves  have  become  well  formed,  and  have  rendered  it  super- 
fluous. In  early  stages  it  must  be  regarded  as  the  principal  valve  of  the 
heart.  The  tricuspid  valve,  between  the  right  atrium  and  right  ventricle, 
develops  from  the  cardiac  walls  in  the  same  way  as  the  bicuspid  valve. 
Their  formation  is  discussed  by  Mall  (Amer.  Journ.  Anat.,  1912,  vol.  13,' 
pp.  249-298). 

In  the  embryonic  heart,  the  left  atrium  receives  most  of  its  blood 
through  the  foramen  ovale,  but  the  pulmonary  veins  early  grow  out  from 
it  as  a  small  vessel  (Fig.  170,  D)  which  sends  four  branches  to  the  lungs. 
These  are  given  off  near  the  heart,  and  with  the  enlargement  of  the  atrium 
they  come  to  open  into  it  separately.  After  birth  they  are  the  only 
supply  of  the  left  atrium,  and.  they  convey  the  same  quantity  of  blood  as 
the  veins  which  enter  the  right  atrium. 

LAYERS  OF  THE  HEART.  Early  in  the  development  of  the  heart  a 
third  layer,  consisting  of  mesenchyma,  forms  between  the  endothelium 
and  mesothelium.  It  gives  rise  to  the  cardiac  musculature,  and  toward 
the  primary  layers  it  produces  connective  tissue.  The  wall  of  the  heart 


1 78 


HISTOLOGY 


in  the  adult  is  divided  into  three  layers,  the  endocardium,  myocardium 
and  epicardium  respectively.  The  endocardium  consists  of  the  endothe- 
lium,  which  is  continuous  with  that  of  the  blood  vessels,  and  of  subendo- 
thelial  fibrous  tissue.  According  to  Mall,  this  tissue  is  derived  from  the 
endothelium.  The  myocardium  is  the  muscle  layer,  which  is  thin  in  the 
atria,  but  very  thick  in  the  ventricles;  in  the  left  ventricle  it  is  much 
thicker  than  in  the  right.  The  epicardium  consists  of  the  pericardial  epi- 
thelium together  with  underlying  connective  tissue.  This  layer  is  also 
called  the  visceral  pericardium,  and  with  the  parietal  pericardium  it  bounds 
the  pericardial  cavity,  forming  a  closed  sac  containing  the  pericardial 

fluid.  The  general  relations  of 
these  layers  in  an  embryonic 
heart  are  shown  in  Fig.  171. 
The  epicardium  is  a  smooth 
layer.  The  musculature  of  the 
ventricles  is  arranged  in  trabec- 
ulse  covered  with  endothelium, 
between  which  there  are  blood 
spaces  classed  as  sinusoids.  In 
the  adult  the  musculature  is 
more  compact,  but  internally  it 
is  indented  by  many  clefts  and 
irregular  spaces,  extending 
among  the  trabecula  carnea  and 
the  conical  papillary  muscles. 

Endocardium.  The  endo- 
cardium consists  of  endothelium 
which  is  a  single  layer  of  flat, 
irregularly  polygonal  cells,  and 
of  the  underlying  connective 
tissue  which  contains  smooth 
muscle  and  many  elastic  fibers 
(Fig.  172).  Elastic  fibers  are  more  highly  developed  in  the  atria  than  in 
the  ventricles;  they  occur  either  as  networks  of  thick  fibers  or  fuse  to 
form  fenestrated  membranes.  Smooth  muscle  fibers  are  more  numerous 
where  the  wall  of  the  heart  is  smooth;  they  are  most  abundant  in 
front  of  the  root  of  the  aorta. 

The  a  trio- ventricular  valves  are  essentially  folds  of  endocardium 
containing  dense  fibro-elastic  tissue  continuous  with  the  similar  tissue 
in  the  annuli  fibrosi.  The  valves  contain  muscle  fibers  toward  these 
rings,  and  elastic  fibers  which  are  prolonged  into  the  chorda  tendinea. 
Blood  vessels  are  found  only  in  the  basal  portion  of  the  valves,  where  the 
muscle  fibers  occur.  The  semilunar  valves  of  the  pulmonary  artery  and 


mes 


en 


FIG.  171. — SECTION  OF  THE  HEART  SHOWN  IN  FIG.  170,  F. 

ca.,  Capillaries;  en.,  endothelium;  1.  a.,  left  atrium;  1.  v., 
left  ventricle;  mes.,  mesothelium  (of  the  epicardium, 
or  visceral  pericardium) ;  p.  c.,  pericardial  cavity;  j).  p., 
parietal  pericardium;  r.  a.,  right  atrium;  r.  v.,  right 
ventricle;  si.,  sinusoids;  v.  b,  bicuspid  valve;  y.  t., 
tricuspid  valve;  v.  v.  s.,  valves  of  the  venous  sinus. 


HEART 


179 


aorta  contain  neither  muscle  fibers  nor  vessels.  Their  elastic  fibers  are 
found  chiefly  on  the  ventricular  sides  of  the  valve,  and  in  the  noduli 
(which  are  thickenings  in  the  middle  of  the  circumference  of  each  segment, 
to  perfect  their  approximation  when  closed). 

Myocardium.  The  myocardium  consists  of  muscle  fibers  arranged 
in  layers  or  sheets,  which  are  wound  about  the  ventricles  in  complex  spirals, 
making  a  vortex  at  the  apex  of  each  ventricle.  If  the  heart  is  boiled  in 
dilute  acid  these  layers  may  be  unwound,  and  the  heart  has  frequently 
been  investigated  in  this  way,  most  recently  by  Mall  (Amer.  Journ. 
Anat,  1911,  vol.  n,  pp.  211-266).  The  layers  are  composed  of  cardiac 
muscle,  which  is  a  syncytium  of  striated  fibers  with  central  nuclei, and 


Endocardium. 


Endothelium. 


Nuclei  of  con-  a_- 
nective  tissue. 


Connective  f 
tissue  fibers.  I    — 


Detached 
endothelial  cell. 


Small  artery. 


t  Fibers  of  the  atrio- 
ventricular  system. 


Connective  tissue. 


Nucleus  of  a  con- 
nective tissue  cell. 

Nucleus  of 
cardiac  muscle. 
Sarcoplasm. 


-- )  Capillaries. 


FIG.  172. — FROM  A  CROSS  SECTION  OK  THE  PECTINATE  MUSCLES  OF  A  HUMAN  HEART  (RIGHT  ATRIUM). 

X  240. 
The  muscle  fibrils  in  transverse  sections  appear  as  points;  at  x  they  are  radially  arranged. 

intercalated  discs,  as  already  described  (p.  129).  Cardiac  muscle  is  shown 
in  longitudinal  section  in  Fig.  121  (p.  129),  and  in  transverse  section  in 
Fig.  172.  Between  the  muscle  fibers  there  are  capillary  branches  of  the 
coronary  vessels  which  ramify  in  the  epicardium.  The  capillaries  come 
into  close  relation  with  the  muscle  fibers  and  some  of  them  extend  into 
the  endocardium.  Certain  vessels,  especially  in  the  right  atrium,  empty 
into  the  cavity  of  the  heart  as  small  veins  known  as  the  vence  minima 
(or  veins  of  Thebesius).  Minute  veins  in  the  papillary  muscles  have 
been  described  as  opening  into  the  ventricle  at  both  ends. 


i8o 


HISTOLOGY 


In  the  heart  of  adult  frogs,  the  system  of  intermuscular  clefts  or  lacunar  vessels 
is  the  only  blood  supply  of  the  ventricular  musculature;  the  coronary  vessels  are 
limited  to  the  epicardium.  In  turtles  the  coronary  vessels  supply  an  outer  layer  of 
the  ventricular  muscles,  but  the  greater  part  is  still  nourished  by  the  central  lacunae 
or  sinusoids.  This  sinusoidal  circulation,  which  is  characteristic  of  the  adult  heart 
in  lower  vertebrates,  occurs  also  in  mammalian  embryos,  but  it  becomes  vestigial  in 
adult  mammals. 


Yes 


Rd 


A  structure  which  has  recently  received  much  attention  because  of  its 
functional  importance  is  a  small  band  of  muscle  fibers,  associated  with 
nerves,  which  passes  from  the  septum  between  the  atria  into  the  septum 
between  the  ventricles.  This  atria-ventricular  bundle  or  " bundle  of  His" 

(discovered  independently  in 
1893  by  Kent  and  His,  Jr.) 
represents  the  only  connec- 
tion between  the  muscula- 
ture of  the  atria  and  ventri- 
cles; it  passes  through  the 
fibrous  tissue  where  the 
annuli  fibrosi  come  together. 
The  position  of  the  bundle 
is  shown  in  Fig.  173,  after 
Curran  (Anat.  Rec.,  1909, 
vol.  3,  pp.  618-632).  Curran 
finds  more  extensive  branches 
in  the  atria  than  others  have 
shown.  They  come  from 
both  sides  of  the  heart  into 
the  inter-atrial  septum,  and  converge  from  the  fossa  ovalis,  the  roots 
of  the  tricuspid  valve  and  the.  orifice  of  the  coronary  sinus  to  form 
the  atrio-ventricular  node.  This  is  "a  small  mass  of  interwoven  fibers 
in  the  central  fibrous  body  of  the  heart,"  and  the  main  bundle,  2-3 
mm.  wide,  passes  from  it  into  the  inter-ventricular  septum.  It  passes 
under  the  pars  membranacea,  and  divides  into  two  branches  which  are 
distributed  to  the  right  and  left  ventricles,  respectively.  Their  extensive 
ramifications  have  been  modelled  by  Miss  DeWitt.  .She  describes  the 
models,  and  briefly  summarizes  previous  investigations  of  the  bundle,  in 
the  Anatomical  Record  (1909,  vol.  3,  pp.  475-497);  the  Subject,  is  more 
fully  considered  by  Aschoff  (Verh.  d.  deutsch.  path.  Gesellsch.,  1910, 

PP-  3"35)- 

The  atrio-ventricular  bundle  is  composed  of  muscle  fibers  which  are 
pale  macroscopically.  They  are  larger  than  those  of  ordinary  cardiac 
muscle,  but  contain  fewer  fibrils,  peripherally  placed  and  surrounded 
by  abundant  scaroplasm  (Fig.  172).  In  the  ventricle  they  are  specially 


\F.a.y 


FIG.  173. — THE  ATRIO-VENTRICULAR  BUNDLE  (F.  a.  v.),  AND 

THE  POSITION  OF  THE    "  SlNO-ATRIAL     NODE"    (x)     IN    A 

HUMAN  HEART.     (After  Curran  and  Aschoff.) 
Ao.,  Aorta;  A.  p.,  pulmonary  artery;  F.  o.,  fossa  ovalis;  S.  c., 
coronary  sinus;  R.  d.,  right  branch  of  the  atrio-ventricular 
bundle;  and  R.  s.,  its  left  branch;  V.  c.  i.,  vena  cava  in- 
ferior; V.  c.  s.,  vena  cava  superior. 


HEART  181 

rich  in  glycogen.  In  the  node,  however,  according  to  Miss  DeWitt,  the 
fibers,  though  varying  greatly  in  size,  are  much  smaller  than  those  found 
elsewhere  in  the  heart.  Several  of  them  unite  at  a  point,  producing  stel- 
late groups,  and  the  entire  node  is  an  intricate  network. 

The  fibers  of  the  atrio-ventricular  bundle  resemble  those  described  by  Purkinje 
in  the  sheep,  horse,  cow  and  pig,  but  which  he  could  not  find  in  the  rabbit,  dog  and  man 
(Arch.  f.  Anat.,  Physiol.  u.  wiss.  Med.,  1845,  PP-  281-295).  In  the  walls  of  the  ven- 
tricle, immediately  beneath  the  endocardium,  he  observed  "first  with  the  naked  eye,  a 
network  of  gray,  flat  gelatinous  threads,  which  in  part  were  prolonged  into'the  papillary 
muscles,  and  in  part  passed  like  bridges  across  the  separate  folds  and  clefts."  Under 
the  microscope,  they  appeared  very  granular,  but  he  decided  that  they  were  probably 
muscular.  Purkinje's  fibers  are  regarded  as  imperfectly  developed  muscle  fibers. 
In  the  human  heart  they  are  not  as  distinct  from  the  other  cardiac  muscle  fibers  as  in 
the  sheep.  It  is  possible  that  they  are  directly  continuous  with  the  cardiac  syncy- 
tium,  although,  as  noted  by  Miss  DeWitt,  if  the  transition  is  gradual  it  will  be  very 
difficult  to  observe  in  sections. 

At  the  junction  of  the  superior  vena  cava  and  the  atrium,  Keith  and 
Flack  have  described  a  peculiar  musculature  imbedded  in  densely  packed 
connective  tissue,  composed  of  striated,  fusiform  fibers,  plexiform  in  ar- 
rangement, with  well-marked  elongated  nuclei,  "in  fact,  of  closely  similar 
structure  to  the  node"  (Jo urn.  Anat.  and  Physiol.,  1907,  vol.  41,  pp. 
172-189).  These  fibers  are  said  to  be  in  close  relation  with  the  vagus  and 
sympathetic  nerves;  they  have  a  special  arterial  supply.  According  to 
Keith  and  Flack  they  are  situated  at  the  junction  of  the  sinus  venosus 
and  the  atrium,  and  they  form  the  sino-atrial  node  (sino-auricular  node). 
The  sino-atrial  node  is  found  immediately  beneath  the  epicardium  in  the 
position  shown  in  Fig.  173.  In  it  the  impulse  for  the  heart  beat  is  be- 
lieved to  originate,  and  to  be  transmitted  to  the  atrio-ventricular  node; 
the  latter  correlates  the  contraction  of  the  atrium  with  that  of  the 
ventricle. 

Epicardium.  The  epicardium  is  a  connective  tissue  layer,  covered 
with  simple  flat  mesothelium  and  containing  elastic  fibers  and  many  fat 
cells.  The  latter  are  distributed  along  the  course  of  the  blood  vessels. 

Vessels  and  Nerves.  The  branches  of  the  coronary  vessels  pass  from 
the  epicardium  into  the  myocardium,  forming  capillaries  in  intimate 
relation  with  the  muscle  fibers.  The  heart  is  thus  supplied  with  aerated 
blood  from  the  root  of  the  aorta,  as  well  as  by  the  blood  within  its  own 
cavities;  on  the  left  side  this  is  aerated,  but  not  on  the  right. 

The  lymphatic  vessels,  draining  toward  the  base  of  the  heart,  are 
very  abundant,  and  true  lymphatic  vessels  are  found  in  all  layers  of  the 
heart.  The  tissue  spaces  in  the  myocardium  are  also  extensive. 

The  nerves  to  the  heart  have  already  been  described  as  forming  the 
cardiac  plexus.  This  plexus  receives  branches  from  the  vagus,  and  from 
the  sympathetic  cardiac  nerves  proceeding  from  the  cervical  sympathetic 


l82  HISTOLOGY 

ganglia.  It  sends  its  fibers  toward  the  heart,  where  they  follow  the 
coronary  vessels  in  their  ramifications.  The  cardiac  ganglion  is  asso- 
ciated with  the  superficial  part  of  the  cardiac  plexus,  and  is  under 
the  arch  of  the  aorta.  Other  small  ganglia  occur  on  the  posterior  wall 
of  the  atria,  and  scattered  ganglion  cells  are  found  along  the  atrio-ven- 
tricular  bundle.  They  have  been  reported  along  the  nerves  elsewhere  in 
the  heart.  The  ganglion  cells  are  probably  in  connection  with  efferent 
fibers  from  the  central  nervous  system,  which  include  two  sorts — fibers 
from  the  ventral  ramus  of  the  accessory  nerve,  which  pass  out  'with  the 
branches  of  the  vagus  and  inhibit  cardiac  action;  and  fibers  from  the 
spinal  nerves,  by  way  of  the  inferior  cervical  ganglion,  which  accelerate  it. 
Histologically  nerve  endings  have  been  seen  both  within  and  around  the 
capsules  of  cardiac  ganglion  cells.  It  is  said  that  the  medullated  nerve 
fibers  from  the  central  system  end  within  the  capsules;  and  that  non- 
medullated  branches  from  adjacent  sympathetic  ganglia  end  outside  of 
them.  Motor  endings  in  contact  with  cardiac  muscle  have  also  been 
found.  Sensory  endings  have  been  described  both  in  the  epicardium 
and  endocardium.  They  consist  of  terminal  ramifications  forming  "  end- 
plates."  Some  of  these  fibers  presumably  connect  with  sympathetic 
cells  near  at  hand;  others  are  terminations  of  afferent  medullated  fibers 
which  are  said  to  pass  to  the  medulla,  along  the  vagus  trunk,  as  the 
"depressor  nerve," 

LYMPHATIC  VESSELS. 

GENERAL  FEATURES.  The  lymphatic  vessels  are  far  less  conspicuous 
than  the  blood  vessels,  but  they  are  no  less  important  and  are  widely 
distributed  throughout  the  body.  Those  which  occur  in  the  mesentery 
and  are  filled  with  a  milky  fluid  after  intestinal  digestion  has  been  going 
on,  are  the  most  conspicuous.  These  "arteries  containing  milk"  were 
observed  by  Erasistratus,  an  anatomist  of  Alexandria  who  died  in  280 
B.  C.,  but  the  observation  was  discredited  by  Galen.  When  Aselli  in 
1622  found  the  white  vessels  in  a  living  dog  which  he  had  opened,  and  had 
shown  by  cutting  into  them  that  they  were  not  nerves,  it  was  essentially 
a  new  and  great  discovery.  Aselli  observed  that  the  vessels  were  filled 
only  after  digestion,  at  other  times  being  scarcely  visible.  He  traced 
them  to  a  mass  of  lymph  glands  which  he  mistook  for  the  pancreas,  and 
believed  that  they  passed  on  into  the  liver  (De  lactibus  sive  lacteis 
venis,  1627).  Years  before  the  physiological  observations  of  Aselli, 
Eustachius  (who  died  in  1574)  had  described  the  main  trunk  of  the 
lymphatic  system  in  his  treatise  on  the  azygos  vein  (De  vena  sine 
pari,  Syngramma  XIII,  Opusc.  anat.,  1707).  He  states  that  from  the 
posterior  side  of  the  root  of  the  left  jugular  vein  (Fig.  174)  "a  certain 


LYMPHATIC  VESSELS 


large  branch  is  given  off,  which  has  a  semicircular  valve  at  its  origin,  and 
moreover  is  white  and  full  of  aqueous  humor." 

"  Not  far  from  its  source,  it  splits  into  two  parts  which  come  together  a  little  further 
on.  Giving  off  no  branches,  and  lying  against  the  left  side  of  the  vertebrae,  having 
penetrated  the  diaphragm,  it  is  borne  along  to  the  middle  of  the  loins.  There,  having 
become  larger  and  folded  around  the  great  artery,  it  has  an  obscure  ending,  not  clearly 
made  out  by  me  up  to  the  present  time." 

The  vessel  so  well  described  by  Eustachius  is  now  known  as  the 
thoracic  duct.     It  has  the  structure  of  a  vein,  and  empties  its  contents  into 
the  blood  at  the  junction  of  the  left  internal  jugular  and  left  subclavian 
veins.     It  receives  branches  from  the  left  side  of 
the  head  and  the  left  arm,   as  well  as  from  the 
trunk  of  the  body.     There  is  a  corresponding  vessel 
on  the  right  side,  known  as  the  right  lymphatic  duct. 
It  drains  the  right  side  of  the  head,  the  right  arm, 
and  adjacent  territory,  emptying  at  the  junction  of 
the   right  internal   jugular   and   subclavian   veins. 
Having  no  connection  with  the  abdominal  lymphatic 
vessels,  however,  it  is  much  smaller  than  the  thoracic 
duct  on  the  left. 

The  connection  between  the  lacteal  vessels  in 
the  mesentery,  seen  by  Aselli,  and  the  thoracic  duct 
observed  by  Eustachius,  was  demonstrated  physio- 
logically by  Pecquet  (Experimenta  nova  anatomica, 
1651).  He  found  a  whitish  fluid  coming  from  the 
vena  cava  superior  of  a  dog  from  which  the  heart 
had  been  excised,  and  observed  that  its  flow  was 
increased  by  pressure  on  the  mesenteries.  Moreover 
he  described  the  receptaculum  chyli,  or  enlargement 
of  the  thoracic  duct  dorsal  to  the  aorta,  which  receives  the  chylous  fluid. 
This  is  now  called  the  cisterna  chyli.  The  distribution  of  the  lymphatic 
vessels,  which  are  ramifications  of  these  main  trunks,  was  followed  out 
by  skillful  injections,  and  the  results  of  such  studies  were  presented  in 
great  folios  by  Mascagni  (1787)  and  Sappey  (1874).  Considered  as  a 
whole  the  lymphatic  system  may  be  compared  with  a  venous  system 
which  has  no  corresponding  arteries;  it  is  composed  entirely  of  afferent 
vessels. 

Recent  anatomical  studies  of  these  vessels  have  been  concerned  with 
their  origin,  and  their  relation  in  the  adult  to  the  surrounding  connective 
tissue.  The  vessels  have  long  been  known  as  absorbents,  and  it  was 
thought  that  they  opened  freely  at  their  distal  ends  into  the  connective 
tissue  spaces;  through  these  openings  they  were  supposed  to  suck  in  the 
tissue  fluid  which  had  escaped  from  the  vessels,  and  the  chylous  fluid, 


FIG.  174. — THE  AZYGOS 
VEIN  (a)  AND  THO- 
RACIC DUCT  (b)  AS 
FIGURED  BY  EUSTA- 
CHIUS. 


1 84 


HISTOLOGY 


charged  with  nutriment,  which  had  entered  the  intestinal  tissues,  and  to 
convey  this  material  back  to  the  blood  vessels.  Thus  the  lymphatic 
vessels  were  described  as  tissue  spaces,  which  had  elongated  and  coalesced 
so  as  to  form  tubes  bounded  by  flattened  connective  tissue  cells,  and 
these  vessels  were  thought  subsequently  to  acquire  openings  into  the 
veins.  Opposed  to  this  conception  is  the  idea  of  Ranvier  that  the 
lymphatic  vessels  are  primarily  connected  with  the  veins.  They  grow 
out  from  the  veins  as  endothelial  sprouts,  which  form  a  closed  system  of 
endothelial  tubes,  anastomosing  freely  with  one  another,  but  never  with 
the  blood  vessels.  Thus  they  are  connected  with  the  veins  by  main  trunks 
comparable  with  the  ducts  of  glands  (Arch.  d'Anat.  micr.,  1897,  vol.  i, 
pp.  69-81).  Fluids  may  pass  through  the  thin  endothelium  almost  as 
readily  as  through  open  orifices,  so  that  functionally  the  distinction  does 
not  appear  to  be  fundamental. 

Ranvier's  interpretation  has  been  defended  by  MacCallum,  on  the  basis  of  histo- 
logical  studies  (Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1902,  pp.  273-291),  and  by 
Miss  Sabin,  from  the  injection  of  the  lymphatic  vessels  in  embryos  (Amer.  Journ. 
Anat.,  1902,  vol.  i,  pp.  367-389).  The  most  convincing  evidence  in  its  favor  has  been 
supplied  by  Clark's  observations  on  the  growth  of  the  lymphatic  vessels  in  the  tails  of 
tadpoles.  The  tadpoles  were  anaesthetized  with  chloretone.  The  membranous  part 


May  16, 
11.30  A.  M. 


May  19, 

II  A.  M. 


May  19. 

II  P.  M. 


FIG.  175- — SUCCESSIVE  STAGES  IN  THE  GROWTH  OF  A  LYMPHATIC  VESSEL  (lym.)  IN  THE  TAIL  OF  A  TADPOLE 
(Rana  paluslris).     Xi35.     (Clark.)     b.  v.,  Blood  vessel;  n.,  nucleus  of  the  lymphatic  vessel. 

of  the  tail  was  then  examined  with  immersion  lenses,  and  certain  of  the  lymphatic 
vessels  were  drawn.  The  animals  were  restored  to  normal  condition  and  were  re-ex- 
amined at  intervals  of  twelve  hours.  The  growth  of  a  given  lymphatic  vessel  was  thus 
demonstrated,  as  shown  in  Fig.  175.  Its  elongation  and  enlargement  were  seen  to  be 
independent  of  the  surrounding  connective  tissue,  through  which  it  made  its  way. 

In  some  eases  a  blood  corpuscle  had  escaped  into  the  intercellular  spaces.  Toward 
such  a  corpuscle  the  lymphatic  vessel  grew,  and  having  reached  it,  the  corpuscle  was 
taken  in  by  the  endothelial  cells  and  transferred  to  the  lumen  of  the  vessel,  through 
which  it  was  seen  to  travel  toward  the  central  vessels.  As  indicated  in  Fig.  175,  the 
nuclei  of  the  living  endothelium  could  be  observed,  and  the  multiplication  of  the  endo- 


LYMPHATIC  VESSELS 


thelial  cells  during  the  growth  of  the  lymphatic  vessel  was  demonstrated  (Anat.  Rec., 
1909,  vol.  3,  pp.  183-198). 

DEVELOPMENT.  The  development  of  the  mammalian  lymphatic  sys- 
tem begins  with  the  formation  of  a  pair  of  very  large  sacs  lined  with 
endothelium,  situated  at 
the  junction  of  the  jugular 
and  subclavian  veins  (Fig. 
176).  These  jugular  lymph 
sacs  were  first  described 
by  Miss  Sabin  (loc.  cit.); 
they  appear  in  human  em- 
bryos measuring  about  10 
mm.  and  are  formed  by 
the  union  of  several  out- 
growths from  the  veins. 
In  slightly  older  embryos, 
another  lymph  sac  is  pro- 
duced at  the  root  of  the 
mesentery,  below  the  place 
where  the  renal  veins 
enter  the  vena  cava  in- 
ferior (Lewis,  Amer.  Journ. 
Anat.,  1902,  vol.  i,  pp. 
229-244).  The  opinion 
that  this  sac  is  a  derivative 
of  the  adjacent  veins  has 
been  confirmed  by  certain 
later  embryological  studies, 
and  by  finding  permanent 
communications  between 
the  lymphatic  and  the 

VenOUS  SVStem  at  the  level    FIG.  176. — LYMPHATIC  VESSELS  AND  VEINS  IN  A  RABBIT  OF  FOUR- 

*  TEEN  DAYS,  EIGHTEEN  HOURS;  14.5  MM.  X  11.5. 

Of   the  renal  Veins  in  adult    The  lymphatics  are  heavily  shaded,  x  being  a  vessel  along  the  left 

vagus  nerve  and  y  along  the  aorta.     The  large  jugular  lymph 
South   American   monkeys  sac  -is  in  contact  with  the  internal  jugular  vein,  In.  J.;  it  passes 

(Silvester,  Amer.  Journ. 
Anat.,  1912,  vol.  12,  pp. 
446-460) .  At  other  places, 
which  must  be  regarded  as 
secondary  centers,  lymphatic  vessels  appear  to  be  derived  from  the  veins 
and  to  become  detached  from  them.  These  vessels  are  seen  in  the 
mesenchyma  as  isolated  spaces,  usually  along  the  course  of  the  veins, 
at  no  great  distance  from  the  jugular  and  mesenteric  lymphatics.  Subse- 
quently they  become  connected  with  one  another  by  endothelial  out- 


to  the  junction  of  the  external  jugular  (Ex.  J.)  and  subclavian 
veins,  the  latter  being  formed  by  the  union  of  the  primitive 
ulnar,  Pr.  UL,  and  external  mammary  veins,  Ex.  M.  The 
mesenteric  sac  is  in  front  of  the  vena  cava  inferior  (V.  C.  I.) 
and  below  the  renal  anastomosis  (R.  A.).  Other  veins  include: 
Az.,  azygos;  V.,  vitelline;  G.,  gastric;  S.  M.,  superior  mesen- 
teric; etc.  The  figures  indicate  the  position  of  the  correspond- 
ing cervical  nerves. 


i86 


HISTOLOGY 


growths,  such  as  extend  from  the  lymphatic  vessels  into  the  peripheral 
tissues  as  described  by  Clark.  The  mesenteric  sac  thus  becomes  connected 
with  the  left  jugular  sac  (symmetrical  connections  with  both  jugular  sacs 
occur  in  some  animals)  and  the  connecting  vessels  constitute  the  thoracic 
duct.  The  cisterna  chyli  is  a  secondary  enlargement  dorsal  to  the  aorta. 
In  the  adult  the  sacs  are  replaced  by  plexuses  of  smaller  vessels. 

^N 

The  origin  of  the  detached  or  apparently  detached  lymphatic  spaces  in  embryos, 
which  precede  the  formation  of  the  well-defined  vessels,  has  been  studied  with  great 
diligence  by  Huntington  (The  Anatomy  and  Development  of  the  Lymphatic  System, 
Mem.  Wistar  Institute,  1911)  and  McClure  (Anat.  Rec.,  1912,  vol.  6,  pp.  233-248), 
to  whose  many  contributions  references  will  be  found  in  the  papers  cited.  They  con- 
sider that  the  lymphatic  spaces  arise  in  large  part  as  mesenchymal  spaces,  but  the 
possibility  suggested  by  Bremer's  recent  work  on  the  blood  vessels,  that  uninjectable 
endothelial  strands  of  great  delicacy  may  pass  to  these  cavities,  has  not  been  set  aside, 
and  further  work  upon  this  subject  is  being  conducted  under  Professor  McClure's 
direction.  The  reasons  which  led  the  writer  to  consider  the  origin  of  the  lymphatic 
vessels  from  mesenchymal  spaces  as  improbable,  were  stated  as  follows  (Amer.  Journ. 
Anat.,  1905,  vol.  5,  pp.  95-120). 


a  b  c 

PIG.  177. — BLOOD  VESSELS  AND  LYMPHATIC  VESSELS  BETWEEN  THE  CIRCULAR  AND  LONGITUDINAL  LAYERS 

OK  SMOOTH  MUSCLE  FIBERS  IN  THE  SMALL  INTESTINE  OF  A  CAT.     X  775- 

a,  d.,  Lymphatic  vessels;  b,  vein;  c,  artery. 


"  i.  The  lymphatic  spaces  do  not  resemble  mesenchyma  even  when  it  is  cedematous, 
but  on  the  contrary,  are  scarcely  distinguishable  from  blood  vessels  (Langer)." 

"2.  After  being  formed,  the  lymphatics  increase  like  blood  vessels,  by  means  of 
blind  endothelial  sprouts,  and  not-by  connecting  with  intercellular  spaces  (Langer, 
Ranvier,  MacCallum,  Sabin)."  The  subsequent  work  of  Clark  is  here  conclusive. 

"3.  In  early  embryos  detached  blood  vessels  may  be  seen  without  proving  that 
blood  vessels  are  mesenchymal  spaces.  These  detached  vessels  are  not  far  from  the 
main  trunks,  from  which  they  may  have  arisen  by^slender  endothelial  strands,  yet 


LYMPHATIC  VESSELS 


I87 
(Subsequently,   Bremer 


FIG.  178. — SILVER  NITRATE  PREPARATION  OF  A  LYMPHATIC 
VESSEL  FROM  A  RABBIT'S  MESENTERY,  SHOWING  THE 
BOUNDARIES  OF  THE  ENDOTHELIAL  CELLS,  AND  A  BULG- 
ING JUST  BEYOND  A  VALVE. 


often  the  connecting  strands  cannot  be  demonstrated." 
demonstrated  such  strands  in  great  abundance.) 

"4.  The  endothelium  of  the  embryonic  lymphatics  is  sometimes  seen  to  be  con- 
tinuous with  that  of  the  veins"  i.e.,  in  certain  places,  as  in  connection  with  the  jugular 
sac,  the  origin  of  the  lymphatic  vessels  from  the  venous  endothelium  can  be  clearly 
seen;  this  fact  is  conclusively  demonstrated  by  Huntington  and  McClure,  who  use 
the  term  " veno-lymphatic "  for  transitional  vessels  (Amer.  Journ.  Anat.,  1910,  vol. 
10,  pp.  177-311). 

LYMPHATIC  VESSELS  IN  THE  ADULT.  In  sections  of  the  intestine  from 
an  animal  in  which  intestinal  digestion  was  in  progress,  lymphatic  vessels 
may  readily  be  found  between 
the  muscle  layers  (Fig.  177). 
Their  walls  are  decidedly 
thinner  than  those  of  blood 
vessels  of  the  same  caliber, 
and  their  contents  are  typi- 
cally a  granular  or  fibrinous 
coagulum  free  from  red  cor- 
puscles, but  containing  an 
occasional  lymphocyte.  It 

must  be  remembered,  however,  that  blood  vessels  seen  in  sections  are 
not  infrequently  empty,  and  that  blood  corpuscles  may  be  taken  into 
the  lymphatic  vessels.  Having  learned  to  recognize  the  lymphatics  in 
such  favorable  situations  as  the  intermuscular  tissue,  one  may  readily 
identify  them  in  the  connective  tissue  layer  internal  to  the  circular 
muscle  of  the  intestine,  and  in  the  connective  tissue  around  the  bron- 
chioles in  the  lung;  in  the 
embryonic  lung  they  are 
very  conspicuous.  They 
may  then  be  sought  for  in 
various  organs,  but  a  sharp 
distinction  must  be  drawn 
between  the  endothelium- 
lined  lymphatic  vessels  and 
the  interfibrillar  tissue  spaces. 
When  prepared  with  silver 
nitrate,  the  outlines  of  the  en- 
do  thelial  cells  are  seen  to  resemble  those  of  blood  vessels  (Fig.  178),  and  in 
the  larger  lymphatic  vessels  the  endothelium  with  the  underlying  connec- 
tive tissue  forms  a  tunica  intima.  These  lymphatics  (0.2-0.8  mm.  in 
diameter),  are  often  composed  of  three  coats,  though  loose  in  texture.  The 
media  contains  circular  smooth  muscle  fibers  and  a  small  amount  of  elastic 
tissue;  and  the  externa  is  composed  of  longitudinal  connective  tissue  and 
scattered  bundles  of  longitudinal  muscle.  Thus  they  resemble  the  veins 


FIG.  179. 

Lymphatic  vessel  from  a  section  of  a  human  bronchus, 
showing  a  valve,  v. ;  distal  to  the  branch,  br.  Bundles 
of  smooth  muscle  fibers  are  seen  at  m.  f. 


l88  HISTOLOGY 

more  closely  than  the  arteries.  Valves  are  very  numerous  in  lymphatic 
vessels.  They  are  shown  in  section  in  Fig.  179.  In  the  small  vessels  the 
valves  are  described  as  folds  of  endothelium,  such  as  would  be  produced 
if  the  distal  part  of  the  vessel  were  pushed  forward  into  the  proximal  part. 
The  vessels  are  often  distended  on  the  proximal  side  of  the  valve,  produc- 
ing bulbous  enlargements,  as  shown  in  Fig.  178.  Owing  to  the  presence 
of  these  valves,  compression  of  tissue  containing  lymphatic  vessels,  or 
the  contraction  of  the  muscles  of  the  media,  causes  an  onward  flow  of  the 
lymph.  The  nerves  to  lymphatic  vessels  are  like  those  of  the  blood 
vessels.  Lymphatics  are  provided  with  vasa  vasorum.  As  shown  by 
Evans  (Amer.  Journ.  Anat.,  1907,  vol.  7,  pp.  195-208)  very  small  lymph- 
atic vessels  are  accompanied  by  blood  capillaries,  and  the  larger  lymphatics 
are  surrounded  by  a  wide-meshed  capillary  network  resting  on  the  outer 
side  of  the  lymphatic  media.  (In  the  same  volume  of  the  Journal,  pp. 
389-407,  Miller  describes  the  network  of  blood  capillaries  around  the 
lymphatic  vessels  of  the  pleura.) 

BLOOD. 

Blood  consists  of  round  cells  entirely  separate  from  one  another,  float- 
ing in  an  intercellular  fluid,  the  plasma.  The  plasma  also  contains  as  a 
regular  and  apparently  important  functional  constituent,  the  blood  plates 
(or  platelets),  together  with  smaller  granular  bodies.  Blood  cells  or  cor- 
puscles are  of  two  sorts,  (i)  red  corpuscles  or  erythrocytes,  which  become 
charged  with  the  chemical  compound,  hcemoglobin,  and  which  lose  their 
nuclei  as  they  become  mature;  and  (2)  white  corpuscles  or  leucocytes,  which 
are  of  several  kinds,  all  of  them  retaining  their  nuclei  and  containing  no 
haemoglobin.  The  redness  of  blood  is  not  due  to  the  plasma,  but  is  an 
optical  effect  produced  by  superimposed  layers  of  the  haemoglobin-filled 
red  corpuscles.  Thin  films  of  blood,  like  the  individual  red  corpuscles 
seen  fresh  under  the  microscope,  are  yellowish  green.  Blood  has  a  charac- 
teristic odor  which  has  been  ascribed  to  volatile  fatty  acids;  it  has  an 
oily  feeling  associated  with  its  viscosity,  an  alkaline  reaction,  and  a  specific 
gravity  said  to  average  in  the  adult  from  1.050  to  1.060. 

RED  CORPUSCLES.  Development.  The  first  cells  in  the  embryonic 
blood  are  apparently  all  of  one  sort,  derived  from  the  blood  islands.  They 
are  large,  round  cells  with  a  delicate  membrane  and  a  pale  granular  pro- 
toplasmic reticulum;  their  relatively  large  nuclei  contain  a  fine  chromatin 
network  with  several  coarse  chromatin  masses.  Haemoglobin  later  devel- 
ops in  their  protoplasm,  giving  it  a  refractive  homogeneous  appearance. 
Stained  with  orange  G  or  eosin  it  is  clear  and  brightly  colored,  generally 
quite  unlike  any  other  portion  of  the  specimen.  Often  the  haemoglobin 
has  been  more  or  less  dissolved  from  the  corpuscles,  which  then  appear 
granular  or  reticular. 


BLOOD  189 

The  developing  red  blood  corpuscles  are  known  as  erythroblasts,  espe- 
cially in  their  younger  stages  when  the  nuclei  are  reticular.  In  later 
stages  the  nuclei  become  densely  shrunken  or  pycnotic,  and  stain  intensely 
with  haematoxylin.  The  entire  cells  become  smaller,  and  are  then  called 
normoblasts.  The  transition  from  an  erythroblast  to  a  normoblast  is 
shown  in  Fig.  180,  a;  during  this  process  the  cells  divide  repeatedly  by 
mitosis. 

It  will  be  noticed  that  the  terms  applied  to  developing  corpuscles  are  compounded 
of  words  which  describe  the  formative  cells,  instead  of  indicating  what  they  produce. 
Thus  erythroblast  signifies  a  red  formative  cell.  Normoblast  (Lat.  norma,  model  or 
type,  and  Gr,  /SXao-rfo)  is  an  objectionable  term  to  designate  a  nucleated  red  corpuscle 
of  the  usual  size  and  form,  in  contrast  with  the  large  megaloblasts  which  occur  in  certain 
diseases  of  the  blood.  Megaloblasts  have  reticular  nuclei  and  presumably  represent 
a  younger  stage  than  the  normoblasts.  A  reform  in  the  nomenclature  of  blood  cells 
based  upon  morphological  principles,  is  advocated  by  Minot  (Human  Embryology, 
ed.  by  Keibel  and  Mall,  1912,  vol.  2),  and  when  agreement  shall  have  been  reached 
regarding  the  relationships  of  the  cells,  it  will  be  possible  to  adopt  a  reasonable 
terminology. 

In  becoming  mature  red  corpuscles  the  normoblasts  lose  their  nuclei. 
Before  they  disappear,  the  pycnotic  nuclei  often  assume  mulberry,  dumb- 
bell, trefoil  or  other  irregular  shapes. 
According  to  older  observations  they  then 
fragment,  and  are  dissolved  within  the 
normoblasts;  but  it  is  now  generally  be- 
lieved that  they  are  extruded  from  the 
cells,  either  in  one  mass  (Fig.  180,  b)  or 
in  detached  portions,  and  that  the  ex- 

i     i  ,    .  ,  iii  FIG.   1 80. — THE   DEVELOPMENT  OF  RED 

truded  nuclei  are  devoured  by  phagocytes.         CORPUSCLES  m  CAT  EMBRYOS. 

rw.       l  r    *i_  i    •    -U       •          •       u  (Howell.) 

llie    lOSS    OI    the    nUClei    begins    in   numan       a,  Successive  stages  in  the    development 
-,  f  .-,  ,  .,         T  v  of  a  normoblast;  b,   the  extrusion  of 

embryos  of  the  second  month.    In  embryos         the  nucleus. 

of  the  seventh  month,  nucleated  corpuscles 

in  the  circulating  blood  have  become  infrequent,  and  after  birth  it  is 

rare  to  find  one,  except  under  pathological  conditions. 

In  withdrawing  from  the  circulating  blood  the  nucleated  red  corpuscles 
do  not  disappear  from  the  body.  Since  1 868  it  has  been  known  that  the  red 
marrow,  found  within  certain-  bones  in  the  adult,  contains  an  abundance 
of  erythroblasts,  which  multiply  by  mitosis.  They  are  the  source  of  the 
new  corpuscles  constantly  entering  the  circulation.  In  certain  diseases 
of  the  blood,  imperfectly  developed  normoblasts  also  leave  the  marrow, 
and  circulate  as  in  the  embryo.  Before  the  marrow  assumes  theblood- 
forming  function,  the  liver  is  thg^hieftomato'poieticorgair!  Beginning 
in  embryos  of  about  7.5  mm.,  and  continuing  until  birth,  erythroblasts 
are  found  between  the  hepatic  cells  and  the  endothelial  cells  of  the  sinu- 
soids, and  in  certain  stages  they  occur  in  vast  numbers.  Toward  birth, 


190 


HISTOLOGY 


however,  the  erythroblasts  in  the  liver  are  no  longer  abundant,  and  in  a 
few  weeks  after  birth  they  are  said  to  disappear  entirely.  Red  blood 
corpusclesarejormed  also  in  the  embryonic^spleen,  though  to  a  less 


some  mammals  the  spleen  normally 
contains  erythroblasts  in  the  adult. 
In  regard  to  the  source  of  the 
erythroblasts  in  the  spleen,  liver 
and  red  marrow,  two  opinions  are 
held.  It  is  well  known  that  ery- 
throblasts and  fully-formed  red 
corpuscles  may  wander  out  of  the 
vessels  into  connective  tissue. 
Accordingly  it  is  often  stated  that 
the  circulating  erythroblasts,  which 
at  first  multiply  in  the  blood  ves- 
sels, later  withdraw  to  the  reticular 
tissue  of  the  liver,  spleen,  and 

marrow  and  there  proliferate.  Others  consider  that  the  erythroblasts 
are  formed  in  situ  in  these  various  places  from  the  endothelial  or  reticular 
tissue  cells. 

Mature  Red  Corpuscles.     In  the  lower  vertebrates,  the  mature  red 


Leucocyte  in 
motion;  at  rest. 


Side  view  of 
red  corpuscles. 


FIG.  181. — BLOOD  CORPUSCLES  FROM  A  FROG. 

4,  5,  and  6,  Surface  views  of  red  corpuscles;  6,  after 

treatment  with  water.     X  600. 


FIG.  182. — RED  CORPUSCLES  FORMING  ROULEAUX.     FIBRIN  IN  FILAMENTS  RADIATES  FROM  THE  BLOOD 
PLATES.    (From  Da  Costa's  Clinical  Haematology.) 

corpuscles  or  erythrocytes  are  oval  nucleated  bodies,  more  or  less  bicon- 
vex, thus  differing  radically  from  those  of  adult  mammals.  They  are 
very  large  in  the  amphibia  (Fig.  181).  When  a  drop  of  freshly  drawn 
mammalian  blood  is  spread  in  a  thin  film  on  a  glass  slide,  beneath  a  cover 


BLOOD  IQI 


glass,  it  is  seen  to  consist  chiefly  of  biconcave  discs,  and  of  those  in  the  form, 
of  shallow  saucers  (Fig.  182).  They  have  a  remarkable  tendency  to  pile 
up  in  rouleaux,  like  rolls  of  coins.  It  is  said  that  discs  of  cork  weighted 
so  that  they  will  float  beneath  the  surface  of  water,  will  come  together  in 
a  similar  way  if  their  surfaces  have  been  coated  with  an  oily  substance. 
If  the  blood  coagulates,  filaments  of  fibrin  will  be  seen  in  the  plasma, 
as  shown  in  the  figure.  In  fresh  specimens  there  is  no  fibrin,  and  within 
the  blood  vessels  it  does  not  form  under  normal  conditions.  Moreover 
when  they  are  within  the  endothelial  tubes,  red  corpuscles  do  not  come 
together  in  rouleaux.  It  is  evident  that  the  thin  film  of  blood,  though 
very  fresh,  is  examined  under  extremely  artificial  conditions;  and  from 
such  preparations,  conclusions  as  to  the  normal  shape  of  the  corpuscles 
should  not  be  hastily  drawn.  Within  the  blood  vessels  the  red  cor- 
puscles are  typically  cup-shaped. 

Rindfleisch  (Arch.  f.  mikr.  Anat.,  1880,  vol.  17,  pp.  21-42)  found  that  the  corpuscles 
in  guinea-pig  embryos,  after  losing  their  nuclei  by  extrusion,  are  at  first  bell-shaped; 
but  he  considered  that  afterward  they  become  biconcave  discs  from  impact  with  others 
in  the  circulating  blood.  Commenting  upon  this  statement,  Howell  (Journ.  of  Morph., 
1890,  vol.  4,  pp.  57-116)  writes: 

"I  feel  convinced  that  the  bell  shape  which  Rindfleisch  ascribes  to  the  curpuscles 
which  have  just  lost  their  nuclei  is  a  mistake.  The  red  corpuscles  even  of  the  circula- 
tion, as  is  well  known,  frequently  take  this  shape  when  treated  with  reagents  of  any 
kind,  or  even  when  examined  without  the  addition  of  any  liquid.  It  seems  very 
natural  to  suppose  that  the  biconcavity  of  the  mammalian  corpuscle  is  directly  caused 
by  the  loss  of  the  nucleus  from  its  interior.  Certainly  as  long  as  the  corpuscles  retain 
their  nuclei,  they  are  more  or  less  spherical,  and  after  they  lose  their  nuclei  they  become 
biconcave." 

In  the  year  preceding  Howell's  publication,  Dekhuyzen  discussed  cup-shaped  cor- 
puscles (Becherformige  rote  Blutkorperchen,  Anat.  Anz.,  1899,  vol.  15,  pp.  206-212) 
which  he  found  as  a  transient  stage  in  mammals,  and  which  his  assistant  saw  in  blood 
drawn  from  his  finger.  Dujardin  (Manuel  de  1'observateur  au  microscope,  1842) 
found  many  corpuscles  shaped  "like  cups,  or  cupules  (acorn  cups)  with  thick  borders" 
in  blood  altered  by  the  action  of  phosphate  of  soda.  The  first  reference  to'  such  forms 
is  by  Leeuwenhoek  (1717)  who  put  a  drop  of  blood  in  a  concoction  of  pareira  brava, 
and  found  that  most  of  the  globules  which  make  the  blood  red,  have  "a  certain  bend 
or  sinus  receding  within,  as  if  we  had  a  vesicle  full  of  water  and  by  pressure  of  the  finger 
should  hollow  out  the  middle  of  the  vesicle  as  a  pit  or  depression."  Von  Ebner,  in 
Koelliker's  Handbuch  (1902),  writes  of  bell  or  cap-shaped  corpuscles  produced  in 
warmed  blood  by  the  thickening  of  the  border  on  one  surface  of  the  disc.  Weidenreich 
in  1902  (Arch.  f.  mikr.  Anat.,  vol.  61,  pp.  459-507)  after  thorough  study  of  blood 
variously  preserved,  and  also  examined  while  circulating  in  the  mesentery  of  a  rabbit, 
concluded  that  "the  red  corpuscles  of  mammals  have  the  form  of  bells  (Glocken)." 
Weidenreich's  conclusion  has  not  been  fully  accepted  by  Jolly,  David,  Jordan,  and 
Schafer.  Schafer  (in  Quain's  Anat.,  vol.  2,  1912)  states  that  "  this  opinion,  although 
shared  by  F.  T.  Lewis,  Radasch  and  a  few  other  histologists,  cannot  be  accepted,  for, 
on  examining  the  circulating  blood  in  the  mesentery  and  other  transparent  parts 
of  mammals,  it  is  easy  to  observe  that,  with  few  exceptions,  the  erythrocytes  are 
biconcave;  this  shape  must  therefore  be  regarded  as  the  normal  one." 


I Q2  HISTOLOGY 

That  the  shape  of  corpuscles  in  the  circulating  blood  is  not  easy  t6  observe,  is  shown 
by  the  fact  that  scientists  have  described  it  in  very  different  ways.  The  circulating 
corpuscles  may  be  seen  by  spreading  the  mesentery  of  an  anaesthetized  guinea-pig 
across  the  condenser  of  a  microscope,  having  it  preferably  in  a  warm  room,  and  then 
placing  a  cover  glass  directly  over  the  vessels;  they  are  examined  with  an  immersion 
lens.  Sketches  made  during  such  observations  are  reproduced  in  Fig.  183..  The 
upper  drawing  shows  a  vessel  stretched  out  abnormally,  and  the  corpuscles  are  corre- 
spondingly elongated;  the  one  at  the  left  shows  the  hollow  of  the  cup  toward  the  ob- 
server, the  others  are  seen  in  lateral  view.  Pre- 
sumably normal  conditions  are  shown  in  the 
lower  sketch,  which  includes  two  flat  corpuscles, 
one  of  which  is  almost  biconcave,  but  this  form 
is  exceptional.  The  corpuscles  are  very  flexible, 
,bending  around  any  obstruction,  and  when  free, 
again  assuming  their  original  form.  They  roll 
about  as  they  flow  through  the  vessels,  and  when, 

FIG.  183. — RED  CORPUSCLES,  SKETCHED     as  the  blood  stagnates,  the  current  in  the  vessels 
WHILE    CIRCULATING   IN   THE    VES-      .  .  .     .    .    .  .  . 

SELS  OF  THE  OMENTUM  OF  A  GUINEA-     is  sometimes  reversed,  their  form  does  not  change. 

In  1903,  following  Weidenreich's  publication,  the 

writer  demonstrated  the  circulating  corpuscles  to  Professor  Minot,  who  describes  the 
cup-shape  as  the  normal  form  in  Keibel  and  Mall's  "Embryology";  and  in  1909  they 
were  shown  to  Dr.  Williams  who  was  convinced  that  they  are  cup-shaped. 

A  very  important  result  of  recent  studies  (which  Schafer  does  not  mention)  is 
the  recognition  that  in  well  preserved  tissues  of  all  sorts,  and  with  all  fixatives  such 
as  are  relied  upon  to  reveal  the  structure  of  other  tissues,  the  mammalian  erythro- 
cytes  are  typically  cup-shaped.  Other  forms  are  exceptional.  In  many  specimens 
the  corpuscles  and  other  tissues  are  irregularly  shrunken,  but  where  the  tissues  in 
general  are  excellently  preserved,  the  corpuscles  appear  as  cups.  The  biconcave 
discs  are  flattened  cups. 

In  examining  films  of  fresh  blood,  the  biconcave  discs  will  be  seen  to 
change  their  appearance  as  the  objective  is  lowered.  When  sharply  in 
focus  the  thin  central  portion  appears  light  (Fig.  184,  A);  but  in  high 
focus  the  center  is  dark,  perhaps  owing  to  the  dispersal  of  light  by  the 
lenticular  .corpuscles.  The  biconcave  shape  is  apparent  when  the  corpuscle 
is  seen  on  edge  (Fig.  184,  B).  The  cup-shaped  forms  are  shown  in  Fig. 
184,  D ;  and  E  represents  one  of  the  innumerable  shapes  due  to  shrinkage. 
The  cups  may  be  irregularly  infolded,  presenting  shapes  which  can  be 
imitated  by  indenting  a  soft  hat.  If  the  corpuscles  are  placed  in  water 
or  a  dilute  solution,  their  haemoglobin  passes  out  and  water  enters,  so 
that  they  are  reduced  to  transparent  membranes  or  shadows  (Fig.  184, 
F).  Such  forms  are  often  seen  in  clinical  examinations  of  urine.  In 
dense  solutions,  and  in  fresh  preparations  as  the  plasma  becomes  thicker 
from  evaporation,  water  leaves  the  corpuscles.  They  then  shrink, 
producing  spiny  or  nodular  round  masses  of  haemoglobin,  known  as 
crenated  corpuscles  (Fig.  184,  G).  A  0.6  per  cent,  aqueous  solution  of 
common  salt  is  said  to  cause  the  least  distortion  from  swelling  or  shrinkage. 
In  life  the  corpuscles  doubtless  change  their  shape,  responding  to  the 


BLOOD 


193 


variations  in  their  haemoglobin  content  and  in  the  surrounding  plasma. 
Occasionally  they  are  spherical  (according  to  Schultze,  and  others),  and 
deviations  from  the  primary  cup-shaped  form  are  to  be  expected.  In 
these  changes  the  corpuscles  act  like  membranes  filled  with  fluid.  In 
the  mature  corpuscles,  however,  the  outer  layer  is  thick,  blending  with 
the  contents  within;  and  since  no  sharp  bounding  line  can  be  seen  histo- 
logically,  the  corpuscles  have  been  described  as  lacking  membranes. 
The  plastic  nature  of  the  membrane  is  shown  by  heating  the  blood  film. 
The  corpuscles  then  become  globular  and  send  out  slender  varicose 
processes,  or  round  knobs  attached  by  pedicles  (Fig.  184,  H).  These 
small  spheres  become  detached  in  great  numbers. 

The  dimensions  of  red  corpuscles  are  quite  constant.  Those  in  human 
blood  average  7.5  /x  in  diameter  and  ordinarily  vary  from  7.2  to  7.8  /*. 
They  sometimes  surpass  these  limits.  In  biconcave  form  they  are  about 
1.6  fj,  thick.  The  cups  average  7  M  in  diameter  and  are  4  /*  in  depth. 


FIG.  184. — RED  CORPUSCLES  IN  VARIOUS  CONDITIONS. 

Spherical  corpuscles  are  said  to  be  5  n  in  diameter.  The  blood  of  mammals 
other  than  man  also  contains  cups  which  become  discs.  The  latter  are 
oval  in  the  camel  group  but  round  in  all  others.  Their  average  diameters 
are  less  than  in  man  (7.3  ju  in  the  dog,  7.48  M  in  the  guinea-pig),  but  the 
species  of  animal  cannot  satisfactorily  be  determined  from  the  diameter 
of  the  corpuscles.  In  a  given  section,  as  already  noted,  the  red  corpuscles 
furnish  a  useful  gauge  for  estimating  the  size  of  other  structures. 

The  number  of  red  corpuscles  in  a  cubic  millimeter  of  human  blood 
averages  five  million  for  men,  and  four  million  five  hundred  thousand  for 
women.  By  diluting  a  small  measured  quantity  of  blood  and  spreading 
it  over  a  specially  ruled  slide,  the  corpuscles  may  be  counted,  and  the 
number  per  cubic  millimeter  calculated.  A  diminished  number  is  of 
clinical  importance. 

Histologically  the  red  corpuscles  usually  appear  as  homogeneous 
bodies,  but  with  special  methods  a  granular  network  has  been  found 
within  them,  which  has  been  interpreted  as  a  reaction  of  the  haemoglobin 
to  reagents,  and  also  as  a  persistence  of  the  protoplasmic  reticulum  of 
the  erythroblasts.  It  occurs  especially  in  newly  formed  corpuscles 
(seen  in  cases  of  anaemia).  Instead  of  a  net,  there  may  be  rings  or  round 
13 


I 94  HISTOLOGY 

bodies,  some  of  which  have  been  considered  to  be  nuclear  remains.  A 
few  coarse  granules  of  uncertain  significance  are  sometimes  conspicuous. 
The  fatty  exoplasmic  layer  which  invests  the  corpuscle  and  serves  as  a 
membrane  is  not  sharply  marked  out  in  stained  specimens;  it  appears  to 
blend  with  the  contents  of  the  corpuscle.  Although  the  corpuscles 
may  pass  out  of  the  vessels  by  "  diapedesis,"  they  are  not  actively 
motile,  and  their  margins  never  present  pseudopodia.  The  characteristics 
of  haemoglobin  may  be  described  as  follows : 

Haemoglobin  is  an  exceedingly  complex  chemical  substance  which  combines  readily 
with  oxygen  to  form  oxyhamoglobin.  To  the  latter  the  bright  color  of  arterial  blood  is 
due.  Venous  blood  becomes  similarly  red  on  exposure  to  air.  Through  the  oxyhaemo- 
globin,  oxygen  is  transferred  from  the  lungs  to  the  tissues.  Haemoglobin  may  be  dis- 
solved from  the  corpuscles  by  mixing  blood  with  ether,  and  upon  evaporation  it  crystal- 
lizes in  rhombic -shapes  which  vary  with  different  animals.  Those  from  the  dog  are 
shown  in  Fig.  185,  4;  in  man  they  are  also  chiefly  prismatic.  Haemoglobin  is  readily 


3  4 


FIG.  185. — i,  Haemin  crystals  and  3,  hsematoidin  crystals  from  human  blood;  2,  crystals  of  common  salt 
(X  560);  4,  haemoglobin  crystals  from  a  dog  (X  100). 

decomposed  into  a  variety  of  substances,  some  of  which  retain  the  iron  which  is  a  part 
of  the  haemoglobin  molecule,  others  lose  it.  Hamatoidin,  considered  identical  with  a 
pigment  (bilirubin)  of  the  bile,  is  an  iron-free  substance  occurring  either  as  yellow  or 
brown  granules,  or  as  rhombic  crystals.  The  crystals  (Fig.  185,  3)  may  be  found  in  old 
blood  extravasations  within  the  body,  as  in  the  corpus  luteum  of  the  ovary.  Hcemo- 
siderin,  which  contains  iron,  appears  as  yellowish  or  brown  granules  sometimes  ex- 
tremely fine,  either  within  or  between  cells.  The  iron  may  be  recognized  by  the  ferro- 
cyanide  test  which  makes  these  minute  granules  bright  blue.  If  dry  blood  from  a  stain 
is  placed  on  a  slide  with  a  crystal  of  common  salt  the  size  of  a  pin-head,  and  both  are 
dissolved  in  a  large  drop  of  glacial  acetic  acid  which  is  then  heated  to  the  boiling  point, 
a  product  of  haemoglobin  is  formed,  called  hamin.  It  crystallizes  in  rhombic  plates  or 
prisms  of  mahogany  brown  color  (Fig.  185,  i).  Such  crystals  would  show  that  a  sus- 
pected stain  was  a  blood  stain,  but  they  afford  no  indication  of  the  species  of  animal 
from  which  it  was  derived. 

The  duration  of  the  life  of  mature  red  corpuscles  is  unknown,  but  is 
supposed  to  be  brief.  They  may  be  devoured  intact  by  phagocytes,  but 
generally  they  first  break  into  numerous  small  granules.  These  may  be 
ingested  by  certain  leucocytes,  or  by  the  peculiar  endothelial  cells  of  the 
liver.  Their  products  are  thought  to  be  eliminated  in  part  as  bile  pig- 
ment. The  destruction  of  red  corpuscles  occurs  especially  in  the  spleen 
and  haemolymph  glands;  to  a  less  extent  in  the  lymph  glands  and  red  bone 
marrow.  Pigmented  cells  in  some  of  these  structures  derive  their  pig- 


BLOOD  IQ5 

ment  from  destroyed  corpuscles.  Sometimes  a  'stippling'  or  granule 
formation  occurs  within  the  corpuscle,  which  has  been  ascribed  to  degenera- 
tion of  the  haemoglobin.  The  dissolution  of  red  corpuscles  is  known 
as  hcemolysis  and  follows  the  injection  of  certain  poisonous  substances 
into  the  blood.  It  occurs  in  various  diseases.  The  study  of  the  effects 
of  mixing  the  blood  of  one  species  of  animal  with  that  of  another,  has  pro- 
vided a  very  perfect  means  of  distinguishing  the  species  from  which  a 
blood  stain  of  unknown  origin  may  have  been  derived.^^ — •— 

WHITE  CORPUSCLES.  The  white  corpuscles  or  leucocytes  are  those 
blood  cells  which  retain  their  nuclei  and  do  not  contain  haemoglobin. 
The  youngest  stages  of  erythroblasts,  according  to  this  definition,  are 
leucocytes,  and  like  other  leucocytes  they  are  derived  from  the  mesoderm. 
In  1890  Howell  wrote,  " Before  1869  it  was  quite  generally  believed  that 
the  red  corpuscles  are  formed  from  the  white  corpuscles — in  fact,  some 
of  the  most  recent  investigations  favor  this  view,  although  the  evidence 
is  so  overwhelmingly  against  it."  It  is  still  advocated  by  foremost  in- 
vestigators of  the  blood,  and  is  referred  to  as  the  "  monophyletic  theory." 
Those  who  believe  in  diverse  origins  of  red  and  white  corpuscles,  and  of 
the  various  forms  of  white  corpuscles,  support  the  "polyphyletic  theory." 

Maximow  (Arch.  f.  mikr.  Anat.,  1909,  vol.  73,  pp.  444-561)  states  that  "the  first 
leucocytes,  the  lymphocytes,  arise  at  the  same  time  and  from  the  same  source  as  the 
primitive  erythroblasts;  the  latter  represent  a  specially  differentiated  form  of  cell,  but 
the  lymphocytes  always  remain  undifferentiated.  Therefore,  like  the  primitive  blood 
cells  from  which  they  directly  proceed,  they  are  undifferentiated  rounded  amoeboid 
mesenchymal  cells."  Weidenreich  (Anat.  Rec.,  1910,  vol.  4,  pp.  317-340)  concludes 
that  "the  old,  original  view  of  the  unified  genetic  character  of  all  blood  cells  proves  to 
be  correct,"  and  he  regards  the  lymphocyte  as  the  primitive  or  young  form  of  white 
corpuscles.  (For  many  other  references,  see  Minot,  in  Keibel  and  Mall's  Human 
Embryology,  vol.  2.) 

Against  the  monophyletic  interpretation,  it  has  been  asserted  that  the  lymphocytes 
of  the  adult  are  a  different  form  of  cell  from  the  primitive  blood  cells,  and  that  they  are 
not  found  in  embryos  until  the  time  when  lymph  glands  develop.  These  arise  rather 
late — in  rabbits  of  25  mm.  and  in  human  embryos  of  40  mm.  (Lewis,  Anat.  Rec.,  1909, 
vol.  3,  pp.  341-353).  According  to  the  polyphyletic  view,  the  lymphocytes  are  first 
formed  from  the  reticular  tissue  in  these  glands  and  from  similar  tissue  elsewhere.  If 
this  is  true,  it  becomes  unnecessary  to  regard  the  lymph  glands  as  organs  for  producing 
young  cells,  and  the  bone  marrow  as  an  organ  for  producing  old  cells.  The  relation  of 
these  organs  to  blood  formation  will  be  considered  in  a  later  chapter. 

The  number  of  white  corpuscles  in  a  cubic  millimeter  of  human  blood 
is  about  eight  thousand.  If  it  exceeds  ten  thousand  the  condition  is  called 
leucocytosis  and  becomes  of  clinical  importance.  There  exists,  therefore, 
normally  but  one  leucocyte  for  five  or  six  hundred  red  corpuscles.  In 
the  circulating  blood  the  two  sorts  are  said  not  to  be  evenly  mixed;  the 
leucocytes  are  more  numerous  in  the  slower  peripheral  part  of  the  blood 
stream,  near  the  endothelium.  The  leucocytes  may  be  divided  into  three 


196  HISTOLOGY 

classes  according  to  their  nuclear  characteristics,  namely,  into  lymphocytes, 
large  mononuclear  leucocytes,  and  polymorphonuclear  leucocytes. 

Lymphocytes  have  already  been  briefly  described  with  the  constituents 
of  connective  tissue  (Fig.  56,  p.  68).  Ordinarily  they  are  small  cells, 
about  the  size  of  red  corpuscles,  4-7.5  n  in  diameter.  Large  ones  may  be 
double  this  diameter.  Their  protoplasm  forms  a  narrow  rim,  sometimes 
almost  imperceptible,  about  the  dense  round  nucleus  (Fig.  186,  A).  The 
chromatin  is  arranged  in  a  network  associated  with  coarse  chromatic 
masses  such  as  cause  a  characteristic  checkered  appearance.  Some  of  the 

masses  rest  against  the  nuclear 
membrane.  Lymphocytes  are 
capable  of  amoeboid  motion  but 
not  to  the  extent  of  the  poly- 

FIG.  1 86. — LEUCOCYTES  AS  SEEN  IN  A  SECTION  OF  Hu-  morphonuclear      type.           They 

MAN  TISSUE  PRESERVED  WITH  ZENKER'S  FLUID. 

A,   Lymphocyte;    B,    large    mononuclear   leucocyte;  C,  lOrm     trom     22     tO     25%    O±     all 

three  polymorphonuclear  neutrophiles.  1 

Large  mononuclear  leucocytes,  sometimes  20  /*  in  diameter,  form  only 
from  i  to  3%  of  the  leucocytes.  They  possess  round,  oval,  slightly 
indented,  or  crescentic  nuclei,  which  are  vesicular  and  usually  eccentric 
in  position.  Their  chromatin  occurs  in  a  few  large  granules;  as  a  whole 
the  nucleus  is  clear  and  pale  (Fig.  186,  B).  The  protoplasm,  which  is 
abundant,  usually  lacks  coarse  granules  or  other  distinctive  features. 
Sometimes  it  contains  a  few  deeply  staining  granules  as  shown  in  one  of 
the  cells  in  Fig.  187,  II.  The  large  mononuclear  leucocytes  are  notably 
phagocytic.  In  certain  respects  they  are  intermediate  between  lympho- 
cytes and  polymorphonuclear  cells,  and  they  were  formerly  known  as 
"transitional  cells."  Apparently,  however,  they  are  derived  directly 
from  the  modified  endothelial  cells  lining  the  sinuses  of  the  lymph  glands, 
and  they  have  sometimes  been  regarded  as  the  youngest  of  the  forms  of 
cells  shown  in  Fig.  186. 

Polymorphonuclear  leucocytes  are  cells  somewhat  larger  than  red  cor- 
puscles, being  from  7.5  to  10  /*  in  diameter.  They  are  characterized 
by  having  nuclei  with  irregular  constrictions  leading  to  an  endless  variety 
of  shapes  (Fig.  186,  C).  The  nodular  subdivisions  may  be  connected  by 
broad  bands  or  by  slender  filaments.  It  is  said  that  in  degenerating  cells 
the  nucleus  becomes  divided  into  several  separate  masses.  Such  forms 
can  properly  be  called  "poly nuclear,"  an  abbreviated  term  which  is  a 
misnomer  as  applied  to  the  ordinary  cells;  "mononuclear"  as  designating 
,the  preceding  types  is  also  unfortunate  since  it  implies  that  others  have 
several  nuclei.  The  irregular  shape  of  the  polymorphous  nuclei  has  been 
ascribed  to  degenerative  changes,  comparable  to  those  seen  in  the  erythro- 
blast  nuclei.  Within  the  concavity  of  the  nucleus  the  centrosome  may 
be  found,  surrounded  by  a  light  area;  usually  it  occurs  as  a  diplosome. 


BLOOD  197 

(In  the  forms  of  corpuscles  with  round  nuclei  eccentrically  placed,  the 
centrosome  is  on  the  side  where  the  protoplasm  is  most  abundant.) 
The  polymorphonuclear  leucocytes  are  actively  amoeboid,  and  particles 
readily  pass  through  their  superficial  layer,  but  like  other  forms  of  leuco- 
cytes they  are  covered  with  a  very  delicate  cell  membrane. 

Max  Schultze  in  the  first  paper  published  in  the  Archiv  fur  mikroskopische  Anato- 
mic (1865,  vol.  i,  pp.  1-42)  described  an  apparatus  for  the  examination  of  microscopic 
specimens  at  the  body  temperature,  which  he  used  in  studying  human  blood.  He  ob- 
served the  active  creeping  movements  of  the  leucocytes,  closely  similar  to  those  of  the 
most  delicate  amoebae,  and  watched  them  take  up  particles  of  carmine  and  other  dyes 
placed  in  a  drop  of  fresh  blood.  "The  act  of  ingestion,"  as  he  describes  it,  "is  accom- 
panied by  no  striking  maneuver."  He  adds  that  he  has  never  seen  special  processes 
sent  out  to  overcome  foreign  bodies,  but  that  the  creeping  corpuscle,  during  its  uniform 
advance,  passes  over  them  and  presses  them  into  its  substance.  He  diluted  the  blood 
with  two-thirds  of  its  volume  of  fresh  cow's  milk,  and  observed  that  the  leucocytes 
moved  with  the  same  rapidity  as  before,  and  ingested  the  oil  globules  which  are  much 
larger  than  the  pulverized  dye-stuff. 

A  fundamental  characteristic  of  polymorphonuclear  leucocytes  is  the 
development  of  distinct  granules  in  their  protoplasm.  They  can  be  seen 
in  fresh  unstained  specimens,  in  which  it  is  evident  that  some  of  the  cells 
contain  coarse  granules,  and  others  fine  granules.  The  lymphocytes 
and  the  large  mononuclear  leucocytes  contain  neither  sort,  'and  are  there- 
fore described  as  non-granular.  In  order  to  study  the  granules  a  drop 
of  blood  is  spread  thinly  over  a  cover  glass  and  dried,  afterward  being 
stained  with  a  "blood  stain/'  which  is  a  carefully  prepared  mixture  of 
acid  and  basic  dyes.  The  details  of  nuclear  structure  are  not  preserved  by 
this  method,  but  the  granules  are  clearly  differentiated  (Fig.  187).  With 
several  of  the  blood  stains  the  fine  granules  are  colored  purple  or  lilac; 
and  the  coarse  granules  are  found  to  be  of  two  sorts,  one  kind  staining 
red  with  eosin,  and  the  other  blue  with  the  basic  dye.  Only  one  sort  of 
granule  occurs  in  a  single  cell. 

Leucocytes  containing  coarse  blue  granules,  which  often  obscure  the 
nucleus,  are  called  mast  cells.  In  order  to  distinguish  between  them  and 
the  mast  cells  of  connective  tissue,  which  contain  similar  granules  (see 
Fig.  55,  p.  68)  those  in  the  blood  are  often  called  mast  leucocytes.  They 
form  only  0.5%  of  the  leucocytes,  and  in  sections  special  methods  are 
required  to  demonstrate  them.  These  cells  have  recently  been  inter- 
preted as  degenerating  forms,  but  their  significance  has  not  been 
fully  established. 

Leucocytes  with  coarse  granules  which  stain  red  with  eosin,  an  acid 
stain,  are  called  eosinophiles  (sometimes  oxyphiles,  or  acidophiles). 
They  constitute  from  2  to  4%  of  the  leucocytes  in  the  blood.  Eosino- 
philic  cells,  apparently  distinct  from  those  of  the  blood,  occur  also  in 
connective  tissue,  and  since  their  granules  are  preserved  by  ordinary 


igS  HISTOLOGY 

methods,  and  eosin  is  a  dye  used  in  routine  examinations,  these  cells  are 
often  seen.  According  to  Weidenreich  the  eosinophilic  granules  are  mi- 
nute fragments  of  red  corpuscles,  or  products  of  their  degeneration,  which 
have  been  ingested.  Badertscher  (Amer.  Journ.  Anat,  1913,  vol.  15, 
pp.  69-86)  finds  that  eosinophiles  are  very  numerous  in  the  vicinity  of 
the  degenerating  muscle  fibers  in  salamanders,  during  the  time  when 
their  gills  atrophy.  He  agrees  with  Weidenreich  that  the  eosinophilic 
granules  are  not  products  of  protoplasmic  activity  but  are  derived  from 


n. 


v. 


nr. 


FIG.  187. — THE  BLOOD   CORPUSCLES.     (WRIGHT'S  STAIN.)     (E.  F.  Faber,  from  Da  Costa's 

Clinical  Hsematology.) 

I,  Red  corpuscles.    II,  Lymphocytes  and  large  mononuclear  leucocytes.  Ill,    Neutrophiles. 
IV,  Eosinophiles.    V,   Myelocytes   (not  found  in  normal  blood).     VI,   Mast  cells. 

material  outside  of  the  cells;  and  he  likewise  finds  that  they  are  taken  up 
by  lymphocytes  which  thus  become  eosinophiles.  Badertscher's  work  is 
of  interest  in  connection  with  cases  of  trichiniasis  in  man,  in  which  the 
number  of  eosinophiles  in  the  blood  becomes  greatly  increased,  and  at  the 
same  time  there  is  extensive  degeneration  of  the  muscles,  caused  by  the 
parasites.  There  is,  therefore,  reason  to  believe  that  eosinophilic  granules 
are  haemoglobin  derivatives/ but,  as  stated  by  Minot,  "  renewed  investiga- 
tion of  the  eosinophiles  in  man  is  very  desirable." 


BLOOD  199 

The  third  type  of  granular  cell,  unlike  the  eosinophiles  and  mast  cells, 
contains  fine  granules,  and  these  stain  purple  or  lilac  by  taking  both  acid 
and  basic  stains  simultaneously.  They  are  called  neutrophiles,  and  form 
between  70  and  72%  of  the  leucocytes  in  the  blood.  They  are  actively 
amoeboid  and  are  the  principal  wandering  cells  of  the  body,  leaving  the 
blood  vessels  more  readily  than  other  forms.  In  suppurative  processes 
they  accumulate  around  the  centers  of  infection,  and  they  are  of  very 
great  clinical  importance. 

SUMMARY  OF  THE  FORMS  OF  LEUCOCYTES. 

Lymphocytes,  22  to  25%  of  the  leucocytes,  are  small  (about  the  size 
of  a  red  corpuscle)  or  large  (perhaps  twice  the  diameter  of  a  red  corpuscle), 
non-granular,  with  round  checkered  nuclei. 

Large  mononuclear  leucocytes,  i  to  3%,  may  be  two  or  three  times  the 
diameter  of  red  corpuscles.  They  are  non-granular,  or  with  few  granules, 
and  have  pale  vesicular  nuclei,  round  or  crescentic. 

Polymorphonuclear  leucocytes,  larger  than  red  corpuscles,  are  gran- 
ular, with  nuclei  variously  constricted  or  bent.  They  include — 

Mast  cells,  0.5%,  with  very  coarse  basophilic  granules  obscuring 

the  nucleus. 

Eosinophiles,  2  to  4%,  with  coarse  eosinophilic  granules. 

Neutrophiles,  70  to  72%,  with  fine  neutrophilic  granules. 

Blood  plates  (Fig.  188)  are  small  granular  bodies  (Kornchenplaques) 

which  were  recognized  as  a  normal  constituent  of  the  blood  by  Schultze 

in  1865.     Previous  references  to  them  occur,  and  Zimmer- 

/|x  mann  described  them  as  "elementary  corpuscles/ '  be- 

<s)     /    X       lieving  that  they  gave  rise  to   red  corpuscles   (Arch.  f. 

'*)  f  j      path.  Anat.,  1860,  vol.  18,  pp.  221-242).     They  are  2-4  p 

in  diameter,  and  between  245,000  and  778,000  have  been 

FIG.  188.— BLOOD     estimated  to  occur  in  a  cubic  millimeter  of  human  blood. 

PLATES  BESIDE 

TOO!*!  C°R"  They  are  readily  reduced  to  granular  debris  in  ordinary 
sections,  but  when  well  preserved  and  properly  stained, 
they  are  found  to  consist  of  a  central  granular  core  and  a  hyaline  outer 
layer.  Often  they  appear  stellate,  and  on  a  warm  stage  they  exhibit 
amoeboid  movements.  They  are  concerned  in  the  clotting  of  the  blood, 
or  thrombus  formation,  and  during  coagulation  threads  of  fibrin  extend 
out  from  them  as  seen  in  Fig.  182.  It  is  possible,  however,  that  they  are 
only  passively  involved  in  this  process.  In  the  amphibia  certain  small 
spindle-shaped  cells  appear  to  be  similarly  related  to  fibrin-formation, 
and  they  are  called  thrombocytes;  the  same  term  is  sometimes  applied  to 
the  blood  plates.  In  blood  clots  several  days  old,  blood  plates  are  still 
found,  indicating  .that  they  have  more  than  a  transient  existence. 


2OO 


HISTOLOGY 


The  source  of  the  blood  plates  has  been  known  to  American  histologists 
for  several  years,  since  they  have  had  the  opportunity  of  examining  prepa- 
rations made  by  J.  H.  Wright  and  described  by  him  in  1906.  The 
specimen  shown  in  Fig.  189  is  one  of  several  which  were  entrusted  to  the 
writer  for  demonstration  at  the  meeting  of  the  American  Association  of 
Anatomists  in  1906;  figures  of  them  are  reproduced  in  color  in  the 
Journal  of  Morphology  (1910,  vol.  21,  pp.  265-278).  Fig.  189  represents 
a  giant  cell  of  the  bone  marrow,  sending  out  .two  processes  or  pseudo- 
podia  into  a  blood  vessel;  the  endothelium  is  interrupted  at  their  place 
of  entrance.  By  the  special  stain  which  Dr.  Wright  perfected,  the  central 
and  large  part  of  the  cytoplasm  of  the  giant  cells  is  seen  to  consist  of  red 
or  violet  granules,  identical  in  form  and  color  with  the  granules  in  the 
center  of  the  blood  plates.  Moreover  the  giant  cells  are  shown  to  have 
a  clear  blue  exoplasmic  layer,  which  sends  out  slender  processes,  and 
this  exoplasm  also  is  identical  in  structure  with  that  of  the  blood  plates. 
Some  of  the  blood  plates  are  free  in  the  vessels;  others  in  rows  or  clumps 
are  still  connected  with  the  giant  cells.  Fig.  189  shows  a  few  detached 


FIG.  189. — GIANT  CELL  FROM  THE  BONE  MARROW  OF  A  KITTEN,  SHOWING  PSEUDOPODIA'EXTENDING  INTO 
A  BLOOD  VESSEL  (V),  AND  GIVING  RISE  TO  BLOOD  PLATES  (bp).     (J.  H.  Wright.) 


plates,  and  one  which  is  budding  off  from  a  pseudopodium,  but  .the  color- 
contrasts  which  make  these  preparations  convincing  are  scarcely  indicated. 
Through  Wright's  investigations  it  has  been  made  clear  that  blood  plates 
are  detached  portions  of  the  cytoplasm  of  the  giant  cells  in  the  bone 
marrow,  and  of  similar  giant  cells  in  the  spleen;  their  granular  center  is 
endoplasm,  and  their  hyaline  border  is  exoplasm. 

According  to  Schafer  (1912)  Wright's  "suggestion"  seems  improbable;  and  the 
blood  plates  may  be  looked  upon  as  minute  cells.  Others  also  have  regarded  the  gran- 
ular endoplasm  as  a  nuclear  structure.  The  blood  plates  are  still  described  by  m  any 
writers  as  fragments  of  disintegrating  white  corpuscles,  or  fragmenting  nuclei  of  red 
corpuscles;  and  Stohr  records  that  their  origin  is  obscure. 


BLOOD  2OI 

Plasma  is  the  fluid  intercellular  substance  of  the  blood.  It  contains 
various  granules,  some  of  which  are  small  fat  drops  received  from  the 
thoracic  duct.  Others  occurring  in  variable  quantity  are  refractive  parti- 
cles, not  fatty,  either  round  or  elongated;  they  are  known  as  haemato- 
conia  (or  haemoconia).  In  ordinary  sections  the  plasma  appears  as  a 
granular  coagulum.  In  the  process  of  clotting,  fibrin  forms  from  the 
plasma,  and  with  the  entangled  corpuscles,  it  constitutes  the  blood-clot; 
the  fluid  which  remains  is  the  serum.  The  process  of  fibrin  formation 
is  of  considerable  histological  interest,  owing  to  a  possible  analogy  with 
fibril  formation  in  connective  tissue. 

LYMPH. 

The  contents  of  the  lymphatic  vessels  is  called  lymph.  This  fluid 
is  not  identical  with  plasma,  or  with  tissue  fluid,  yet  all  three  are  similar. 
Nutrient  material  passes  from  the  plasma  into  the  tissue  fluid  and 
thence  to  epithelial  cel^s;  and  in  return  the  products  of  epithelial  cells 
enter  the  tissue  fluid  from  which  they  may  be  taken  over  either  into 
the  plasma  or  lymph,  first  passing  through  the  endothelial  walls  of  the 
vessels.  Thus  in  the  intestine  much  of  the  absorbed  fat  is  transferred 
across  the  tissue  spaces  to  the  lymphatic  vessels  (lacteals)  within  which 
it  forms  a  milky  emulsion  known  as  chyle.  This  form  of  lymph  mingles 
with  other  varieties  coming  from  the  various  parts  of  the  body,  and 
together  they  are  poured  into  the  plasma  at  the  jugulo-subclavian  junction. 
Histologically  lymph  appears  as  a  fine  coagulum,  containing  lymphocytes 
and  large  mononuclear  phagocytic  cells.  The  cells  are  not  abundant. 
Occasionally  other  forms  of  blood  corpuscles  are  found  in  lymphatic 
vessels,  but  the  lymphocytes  greatly  predominate. 


III.  SPECIAL  HISTOLOGY. 


BLOOD   FORMING  AND   BLOOD    DESTROYING   ORGANS. 

BONE  MARROW. 

Bone  marrow  is  the  soft  tissue  found  within  the  central  cavities  of 
bones.  Its  source  in  the  embryo  is  the  vascular  mesenchyma  invading  a 
cartilage  which  is  being  replaced  by  bone.  Early  in  its  development  it 
contains  osteoblasts  and  osteoclasts,  and  these  cells  may  be  found  in  adult 
marrow,  where  it  is  in  contact  with  the  bone.  The  greater  part  of  the 
mesenchyma  becomes  reticular  tissue  with  fat  cells  intermingled.  The 
meshes  of  the  reticular  tissue  are  occupied  by  an  extraordinary  variety  of 
cells,  most  of  which  are  called  myelocytes  (marrow  cells).  In  ordinary 

sections  the  tissue  of  the  marrow  appears 
to  be  riddled  with  large  round  holes. 
Under  high  magnification  the  holes  are 
seen  to  be  fat  cells,  the  nuclei  of  which 
are  here  and  there  included  in  the  sec- 
tion (Fig.  190.)  The  reticular  tissue 
framework  of  the  marrow  consists  of  flat- 
tened cells,  generally  seen  cut  across;  their 
nuclei  then  appear  slender  and  elongated. 
The  abundant  meshwork  of  fibrils  asso- 
ciated with  these  cells  is  not  apparent  in 
ordinary  sections.  In  the  meshes  are 
found  giant  cells;  premyelocytes;  myelocytes 
which  are  neutrophilic,  basophilic  or  eosino- 
philic;  erythrocytes ;  lymphocytes;  and  ma- 
ture corpuscles  both  red  and  white. 

The  giant  cells  of  the  marrow  have  a  single  polymorphous  nucleus. 
They  have  therefore  been  named  "megakaryocytes,"  in  distinction  from 
the  multinucleate  osteoclasts  or  "polykaryocytes."  The  nucleus  is  so 
large  that  it  may  be  cut  into  several  slices,  and  by  combining  these  it  has 
been  found  that  the  entire  nucleus  is  a  hollow  sphere  with  perforated  walls; 
the  nuclei,  however,  are  very  irregular,  and  some  may  be  of  other  forms. 
With  Wright's  stain  the  protoplasm  clearly  shows  an  outer  hyaline  exo- 
plasm  and  an  inner  granular  endoplasm.  It  has  been- said  that  the  latter 
is  divisible  into  two  concentric  zones,  which  differ  from  the  protoplasm 
within  the  nuclear  sphere.  In  ordinary  preparations  these  details  are 

202 


FIG.  190. — HUMAN  BONE  MARROW. 
e.,  Eosinophilic  myelocyte;  e-b.,  erythro- 
blast;  e-c.,  erythrocyte;  f.  c.,  part  of 
the  protoplasmic  rim  of  a  fat  cell;  g.  c., 
giant  cell;  my.,  neutrophylic  myelocyte; 
n-b.,  normoblast;  pm.,  premyelocyte; 
r.,  reticular  tissue  cell. 


BONE   MARROW 


203 


not  evident  (Fig.  191).  A  large  number  of  centrosome  granules  (over 
one  hundred)  have  been  found,  and  pluripolar  mitoses  have  been  observed. 
A  phagocytic  function  has  been  ascribed  to  these  giant  cells,  but  it  has 
also  been  denied.  Their  origin  is  unknown,  but  is  said  to  be  from  the 
leucocyte  series  of  cells.  Their  important  function  of  producing  blood 
plates  has  already  been  described  (p.  200). 

Premyelocytes  are  cells  with  large  round  vesicular  nuclei  containing 
one  or  two  coarse  chromatin  masses,  and  surrounded  by  basic  protoplasm 
free  from  specific  granules  (Figs.  190  and  191).  These  cells  are  parents  of 

Neutrophile.    Lymphocytes.      Giant  cell. 


inophile. —UlS        *• 


v  V 

Erythroblasts. 


-•  Erythrocyte. 
f 

Neutrophile. 


Mast  cell. 


Erythroblast. 


Premyelocytes. . 
Border  of  a  fat  cell. 


FIG.  191. — ELEMENTS  OF  HUMAN  BONE  MARROW. 

A,  From  the  femur  at  10  years;  B,  from  a  cervical  vertebra  at  19  years;  C,  from  the  femur  at  77  years; 

D,  from  a  rib  at  59  years. 

myelocytes,  and  are  sometimes  called  "myeloblasts" — a  poor  term,  since 
they  do  not  produce  marrow.  Stohr  refers  to  those  in  Fig.  191  as  "plasma 
cells";  others  describe  them  as  primitive  wandering  cells.  Apparently 
they  are  set  free  from  the  reticular  tissue  and  they  may  produce  not  only 
myelocytes  but  also  erythroblasts. 

Myelocytes  are  cells  larger  than  polymorphonuclear  leucocytes,  having 
round  or  crescentic  nuclei  and  protoplasm  containing  a  varying  quantity 
of  specific  granules,  either  neutrophilic,  basophilic,  or  eosinophilic. 
The  young  cells  have  round  nuclei  and  few  granules.  -  The  oldest  become 
the  granular  leucocytes  ready  to  enter  the  blood  vessels.  Several  genera- 
tions, derived  by  mitosis,  intervene  between  the  young  myelocytes  and  the 
mature  leucocytes.  *  Most  of  the  myelocytes  are  finely  granular  and  neu- 


204  HISTOLOGY 

trophilic.  Some  are  coarsely  granular  and  eosinophilic;  others  contain 
the  basophilic  mast  cell  granules,  but  these  are  not  well  preserved  in  ordi- 
nary specimens.  In  certain  diseases  myelocytes  enter  the  circulating 
blood,  and  they  appear  in  smears  as  shown  in  Fig.  187,  p.  198. 

Erythroblasts  are  generally  found  in  clusters,  some  being  young  with 
vesicular  nuclei,  others  being  normoblasts  with  dense  irregular  nuclei,  such 
as  have  already  been  described.  Rarely  a  nucleus  may  be  found  which 
apparently  is  partly  extruded.  Cup-shaped  corpuscles  are  seen  in  the 
tissue  meshes. 

Lymphocytes  are  not  a  conspicuous  element  of  the  marrow,  yet  they 
are  present  and  sometimes  in  disease  become  abundant. 

The  relations  of  the  blood  vessels  to  the  reticular  tissue  are  of  great 
interest.  It  has  been  thought  that  the  endothelium  blends  with  the  retic- 
ulum  so  that  no  sharp  distinction  can  be  made  between  the  two.  It 
seems  more  probable  that  the  endothelium  is  merely  more  permeable 
than  usual,  by  a  freer  separation  of  its  cells.  The  same  problem  is  pre- 
sented by  the  blood  vessels  and  reticular  tissue  of  the  lymph  glands  and 
spleen. 

The  functions  of  the  marrow  are  the  production  and  dissolution  of 
bone,  the  storing  of  fat,  the  formation  of  granular  leucocytes  (neutrophiles, 
eosinophiles,  and  mast  cells),  of  red  corpuscles,  and  to  a  less  extent  of 
lymphocytes;  to  these  some  would  add  the  destruction  of  red  corpuscles, 
as  indicated  by  ingested  fragments  and  intercellular  granules. 

LYMPH  NODULES  AND  LYMPH  GLANDS. 

The  lymph  glands  arise  as  nodules  of  dense  tissue  in  close  relation 
with  an  artery,  a  vein  and  a  lymphatic  vessel,  as  seen  in  the  photographs, 
Figs.  192  and  193.  The  first  distinct  lymph  glands  in  the  body  are  a  pair 
in  the  axillary  region,  a  pair  in  the  iliac  region,  and  a  pair  or  two  in  the 
maxillary  region.  They  are  found  in  rabbit  embryos  of  about  30  mm., 
and  in  human  embryos  of  about  40  mm.  These  first  glands  are  soon  fol- 
lowed by  others  in  their  vicinity,  producing  axillary,  inguinal  and  cervical 
groups,  respectively;  and  scattered  glands  more  peripherally  situated 
along  the  vessels  develop  later.  At  the  same  time,  the  tissue  around  the 
jugular  and  mesenteric  lymph  sacs  becomes  transformed  into  dense  lym- 
phoid  tissue,  which  is  resolved  into  the  chains  of  deep  lymphatic  glands. 
These  acquire  a  structure  similar  to  that  of  the  superficial  glands.  There 
is  no  satisfactory  evidence  that  the  dense  lymphoid  tissue  of  which  the 
glands  are  composed  is  produced  by  the  emigration  of  cells  from  either  the 
arteries,  veins  or  lymphatics  associated  with  them. 

In  further  development  the  lymph  glands  become  organized  as  shown 
in  the  diagrams,  Figs.  194  and  195.  The  left  half  of  each  diagram  >  repre- 


LYMPH   GLANDS  205 

sents  a  younger  stage  than  the  right  half.  These  instructive  figures  were 
prepared  by  Stohr  on  the  basis  of  Kling's  studies  (Arch.  f.  mikr.  Anat., 
1904,  vol.  63,  pp.  575-610).  In  the  youngest  stage  (Fig.  194)  it  is  seen 
that  the  blood  vessels  enter  and  leave  the  gland  on  one  side,  at  a  place 
called  the  hilus  (Lat.  hilum,  a  small  thing,  applied  to  the  eye  of  a  bean, 
and  to  similar  hollows  in  bean-shaped  organs).  The  lymphatic  vessel, 
as  a  plexiform  peripheral  sinus,  encircles  the  entire  structure.  After 
the  gland  has  enlarged,  lymphatic  vessels  extend  into  the  mass  of  lymphoid 
tissue,  as  shown  on  the  right  of  Fig.  194,  and  eventually  they  pass  clear 


f        \  •         F-i  \m 

mm^W^iw  i 

-  -  ^r;--  -^4  ,^4%|Ul.a 

1       I 


FIG.  192. — THE  FIRST  AXILLARY  LYMPH  GLAND  OF  FIG.  193. — ONE  OF  THE  EARLIEST  CERVICAL  LYMPH 
THE  RABBIT.  FROM  AN  EMBRYO  OF  TWENTY  GLANDS.  FROM  A  HUMAN  EMBRYO  OF  42 
DAYS,  29  MM.  X  60.  MM.  X  60. 

a,  Artery;  g,  lymph  gland;  1,  lymphatic  vessel;  v,  vein. 


through  it  in  a  system  of  anastomosing  sinuses.  The  lymph  then  flows 
into  the  gland  from  the  periphery,  and  out  at  the  hilus;  both  the  afferent 
and  efferent  vessels  are  shown  in  Fig.  195.  Finally  a  connective  tissue 
capsule  develops  around  the  larger  glands,  and  in  some  of  them  it  extends 
into  the  interior,  producing  a  system  of  supporting  trabeculce,  either  round 
or  lamellar.  These  may  unite  with  one  another  as  shown  on  the  right  of 
Fig.  195.  When  present  within  the  gland  they  are  always  found  in  the 
central  axes  of  the  lymph  sinuses. 

By  the  production  of  the  internal  lymph  sinuses,  the  substance  of  the 
gland  is  subdivided  into  rounded  nodules  and  elongated  cords  of  lymphoid 
tissue.  The  nodules  are  found  at  the  periphery  of  the  gland  and  col- 
lectively they  form  its  cortex;  the  cords  constitute  the  medulla.  Several 
other  organs,  e.g.,  the  kidney  and  suprarenal  glands,  are  divided  into  an 
outer  cortex  (bark)  and  an  inner  medulla  (pith).  In  the  center  of  each 
cortical  nodule  there  is  often  a  light  spot,  seen  with  low  power,  which 
constitutes  the  germinal  center.  These  general  features  of  a  lymph 
gland  are  shown  in  Fig.  196.  It  is  evident  that  certain  of  the  secondary 


2O6 


HISTOLOGY 


nodules  in  the  cortex  are  imperfectly  separated  from  one  another,  and  that 
they  are  continuous  below  with  the  anastomosing  medullary  cords. 

The  lymph  glands  of  the  adult  (lymphoglandula,  also  called  Jymph  nodes) 
are  round  or  reniform  structures  varying  in  length  from  a  few  millimeters 


Lymphoid  tissue 


Afferent  lymphatic  vessels. 


/         Blood  vessels. 


Lymphatic  vessel.  Lymphatic  vessel. 

FIG.  194. 


Peripheral 
lymph  sinus. 


Capsule. 


Lymph  sinus. 


Afferent  lymphatic  vessels. 


Lymph  sinus. 


Capsule. 


Secondary 
nodule. 


Trabecula. 


Efferent  lymphatic  vessels. 
FIG.  195. — DIAGRAMS  REPRESENTING  FOUR  STAGES  IN  THE  DEVELOPMENT  OF  LYMP^  GLANDS. 

to  a  few  centimeters.  The  largest  of  them  show  trabeculae  and  are  sub- 
divided into  cortex  and  medulla  as  above  described;  the  small  ones  remain 
permanently  in  the  various  developmental  stages  shown  in  Figs.  194  and 
195.  The  smallest  structures  consist  of  but  a  single  nodule,  with  or  with- 
out a  germinal  center;  it  contains  a  simple  capillary  network  in  its  interior, 


LYMPH   GLANDS 


207 


and  a  lymphatic  plexus  over  its  surface.  Such  solitary  nodules  occur  in 
the  mucous  membranes  of  various  organs.  By  contact  with  one  another 
laterally  they  constitute  the  noduli  aggregati,  or  "Payer's  patches"  of 
the  small  intestine,  which  are  macroscopic  structures  1-5  cm.  long. 
Lymphoid  nodules  irregularly  massed  about  epithelial  pits  become  the 
essential  tissue  of  the  tonsils.  Wherever  it  occurs,  lymphoid  tissue  has 
essentially  the  same  structure  as  that  observed  in  the  lymph  glands. 


,.   ••  Sinus. 


Capsule 


Trabeculse. 


.-•-"  Medullary 
substance. 


"  Fat. 


FIG.  196. — LONGITUDINAL  SECTION  OF  A  HUMAN  CERVICAL  LYMPH  GLAND.     Xi2. 

Lymphoid  tissue  (formerly  called  adenoid  tissue)  consists  of  a  frame- 
work of  reticular  tissue  (see  Fig.  50,  p.  61,  and  the  accompanying  de- 
scription), together  with  detached  cells,  chiefly  lymphocytes,  which  fill 
its  meshes.  Eosinophiles  and  the  various  forms  of  blood  corpuscles 
brought  in  by  the  blood  vessels,  are  present  in  small  numbers.  The  lym- 
phocytes are  like  those  of  the  blood,  and  the  lymph  glands  are  centers  for 
their  production.  Stained  with  haematoxylin,  lymphoid  tissue,  because 


208 


HISTOLOGY 


Lymph  \' 
sinuses.  *" 


of  the  preponderance  of  nuclear  material,  is  very  dark,  and  its  appearance 
even  under  low  magnification  is  quite  characteristic;  it  is  shown  in  the 
medullary  cords  in  Fig.  197,  which  illustrates  also  its  relation  to  the 
lymph  sinuses. 

The  lymph  sinuses  are  not  well-defined  endothelial  tubes,  but  appear 
rather  as  washed-out  portions  of  the  reticular  tissue.  If  the  endothelial 
tubes  which  line  the  lymphatic  vessels  enter  the  lymph  gland  to  form  the 
sinuses,  it  must  be  considered  that  their  cells  separate  and  that  strands 
of  reticular  tissue  pass  across  them.  Some  authorities  consider  that  the 
endothelial  tissue  blends  freely  with  the  reticular  tissue,  so  that  any 
distinction  is  here'  arbitrary.  The  reticular  tissue  cells,  or  endothelial 
cells,  lining  the  sinuses  are  highly  phagocytic,  and  ingested  fragments 
may  be  seen  within  them  in  sections.  Certain  of  these  cells  become  de- 
tached, and  there  is  reason  to 
believe  that  they  are  the  source 
of  the  large  mononuclear  leuco- 
cytes. Lymphocytes  from  the 
adjacent  cords  and  nodules 
also  enter  the  lymph  as  it 
passes  through  the  sinuses, 
and  thus  they  are  added  to 
the  circulation.  Within  the 
cords  and  nodules  they  are 
enclosed  in  a  closer  meshed 
reticulum  than  that  of  the 
sinuses,  which  may  prevent 
them  from  escaping  too  freely. 
The  germinal  centers  con- 
tain cells  with  larger  and  paler 
nuclei  than  those  of  lympho- 
cytes. These  central  cells 
resemble  premyelocytes,  and 
they  are  supposed  to  give  rise  to  lymphocytes.  Mitotic  figures  are  abun- 
dant. The  germinal  centers,  however,  are  not  found  in  certain  nodules, 
and  they  are  absent  from  the  medullary  cords.  This  has  been  explained 
as  due  to  the  slower  and  more  scattered  multiplication  of  cells  in  those 
places,  but  the  germinal  centers  are  absent  also  from  the  early  stages  of 
embryonic  glands.  Presumably  they  are  not  adequately  explained  by 
stating  that  they  are  centers  for  lymphocyte  production. 

The  capsules  of  the  lymph  glands  consist  of  fibrous  connective  tissue, 
containing  elastic  elements  which  increase  in  abundance  with  age. 
Smooth  muscle  fibers  are  present  as  scattered  cells  or  as  slender  bundles. 
The  trabeculae,  which  are  extensions  of  the  capsule,  are  composed  of  the 


FIG.  197. — FROM  THE  MEDULLA  OF  A  LYMPH  GLAND  OF  AN 
Ox.  X  240. 


LYMPH   GLANDS 


209 


same  tissues.  They  are  completely  surrounded  by  the  lymph  sinuses  as 
shown  in  Fig.  197.  The  flat  cells  over  their  surfaces  may  be  regarded  as 
endothelial  cells. 

The  blood  vessels  of  a  lymph  gland  enter  chiefly  at  the  hilus,  but  in 
the  larger  glands  some  of  them  come  in  from  the  periphery  and  run  in 
the  trabeculae;  others  however  pass  out  through  the  trabeculae  into  the 
capsule.  The  principal  artery  enters  at  the  hilus  and  divides  at  once 
into  several  branches,  which  travel  in  the  trabeculae  for  a  short  distance, 
and  then  pass  over  into  the  medullary  cords.  They  extend  through  the 
axes  of  the  cords  into  the  nodules,  giving  off  small  branches  which  form 
a  venous  network  at  the  periphery  of  these  structures.  The  veins  which 
drain  this  network  soon  cross  the  sinuses  and  .enter  the  trabeculae,  in 
which  they  travel  toward  the  hilus  alongside  the  arteries  (Calvert,  Anat. 
Anz.,  1897,  vol.  13,  pp.  174-180).  A  central  artery  surrounded  by  lymph- 
oid  tissue  and  drained  by  peripheral  veins  is  found  not  only  in  lymph 
glands,  but  also  in  the  spleen. 

Nerves  to  the  lymph  glands  are  not  abundant.  They  consist  of  medul- 
lated  and  non-medullated  fibers,  which  form  plexuses  about  the  blood 
vessels,  and  supply  the  muscle  cells  in  the  capsule  and  trabeculae.  They 
have  not  been  found  in  the  nodules  and  cords. 

The  function  of  the  lymph  glands  is  not  only  to  produce  lymphocytes 
which  enter  the  lymphatic  vessels  and  are  conveyed  through  the  thoracic 
duct  into  the  blood,  but  also  to  " filter  the  lymph."  If  certain  poisonous 
substances,  inert  particles,  or  bacteria  are  brought  to  the  gland  in  the 
lymph,  they  may  be  removed  by  the  phagocytic  endothelial  or  reticular 
tissue  cells.  The  gland  at  the  same  time  may  become  enlarged  by  con- 
gestion, and  by  multiplication  of  its  cells. 

H^EMOLYMPH  GLANDS. 

Haemolymph  glands  resemble  small  lymph  glands,  ranging  in  size 
from  a  "  pin-head  to  an  almond."  They  occur  especially  in  the  retro- 
peritoneal  tissue  near  the  origin  of  the  superior  mesenteric  and  renal  ar- 
teries, but  are  found  elsewhere,  and  it  has  been  said  that  their  distribution 
coincides  with  that  of  ordinary  lymph  glands.  They  are  darker  than  the 
lymph  glands,  and  on  section  yield  blood  in  place  of  lymph.  No  lymph- 
atic vessels  are  associated  with  them,  when  typically  developed,  and  in- 
stead of  a  lymph  sinus  they  possess  a  similar  structure  filled  with  blood, 
the  blood  sinus.  The  lymphoid  tissue  with  its  blood  supply,  together  with 
the  capsule  and  trabeculae,  are  like  the  corresponding  structures  in  lymph 
glands.  The  capillary  blood  vessels,  however,  are  readily  permeable, 
so  that  their  contents,  both  plasma  and  corpuscles,  escape  into  the  blood 
sinus.  The  haemolymph  gland  is  therefore  a  "blood  filter."  Many 


2IO 


HISTOLOGY 


blood  corpuscles  fragment  in  passing  through  it,  and  are  removed  from  the 
circulation  by  phagocytic  cells,  which  in  consequence  become  pigmented. 
The  eosinophilic  cells  which  are  found  in  haemolymph  glands  have  been 
explained  as  due  to  the  ingestion  of  haemoglobin  products,  but  it  has 
been  questioned  whether  these  cells  are  more  abundant  than  in  ordinary 
lymph  glands.  A  second  function  of  the  haemolymph  glands,  depending 
upon  the  lymphoid  tissue  around  their  arteries,  is  the  production  of 
lymphocytes  which  may  enter  the  blood  vessels  directly. 

According  to  von  Schumacher  (Arch.  f.  mikr.  Anat.,  1912,  vol.  81,  pp.  92-150)  the 
haemolymph  glands  begin  their  development  like  ordinary  lymph  glands,  but  after  the 
formation  of  the  peripheral  sinus,  the  connections  with  afferent  and  efferent  lymphatic 
vessels  are  lost.  He  finds  various  intermediate  forms  between  the  lymph  and  haemo- 
lymph glands,  depending  upon  the  extent  of  atrophy  of  the  lymphatic  connections,  and 
the  extent  to  which  blood  escapes  from  the  intraglandular  vessels.  After  accidents 
accompanied  by  extravasations  of  blood,  the  sinuses  of  ordinary  lymph  glands  may  be- 
come filled  with  red  corpuscles,  conveyed  to  them  by  the  afferent  lymphatic  vessels. 
Such  glands  differ  obviously  from  the  true  haemolymph  glands,  which  structurally  and 
functionally  are  intermediate  between  lymph  glands  and  the  spleen. 

SPLEEN. 

The  spleen,  being  five  or  six  inches  long  and  four  inches  wide,  is  much 
the  largest  organ  of  the  lymph  gland  series.  It  is  the  first  of  them  to  de- 
velop, appearing  in  rabbits  of  14  days  (10  mm.)  as  a  condensation  of  the 
mesenchyma  in  the  dorsal  mesentery  of  the  stomach.  At  this  stage  the 


A  B 

FIG.  198. — DIAGRAM  OF  A  ILEMOLYMPH  GLAND,  A,  AND  OF  A  PART  OF  THE  SPLEEN,  B. 
The  arteries  are  shown  as  slender  lines  (art.)  and  the  veins  as  heavy  ones  (v.);  c.,  capsule;  b.  s.,  blood 
sinus,  corresponding  with  the  splenic  pulp,  p.;  s.  n.,  secondary  nodule;  sp.  n.,  splenic  nodule;  tr., 
trabecula. 

only  lymphatic  vessels  in  the  embryo  are  those  near  the  jugular  vein. 
Lymph  glands  are  not  indicated  until  six  days  later.  The  blood  vessels 
enter  the  spleen  at  its  hilus  and  branch  freely.  In  early  stages  they  form 
an  ordinary  capillary  plexus,  but  subsequently  their  walls  become  so  per- 
vious that  most  of  the  blood  escapes  into  the  reticular  tissue  in  passing 


SPLEEN 


211 


from  the  artery  to  the  vein.  Surrounding  the  arterial  branches  there 
is  a  zone  of  lymphoid  tissue,  which  arises  rather  late  in  embryonic  life. 
In  reptilian  spleens  it  is  so  abundantly  developed  that  the  organs  resemble 
mammalian  haemolymph  glands.  In  the  guinea-pig  the  lymphoid 
sheath  of  the  arteries  is  continuous,  though  narrow;  in  man  it  is  so  inter- 
rupted as  to  form  a  succession  of  spindle-shaped  or  spherical  masses, 
called  splenic  nodules  (Malpighian  corpuscles).  An  arterial  branch 
passes  through  each  nodule.  Thus,  as  compared  with  the  haemolymph 


Terminal  vein. 


Sheathed  artery.        Pulp  artery. 


Pulp  vein. 


Beginning  of  a 
trabecular  vein. 


Capillaries  of 

a  nodule.      }i 


Trabecula. 


Penicillus. 


Central  artery. 


Splenic 
lobule. 


Trabecular  vein. 


Trabecular 
artery. 


Hilus.  Reticulum.        Splenic  noudle. 

Capsule. 

FIG.  199. — DIAGRAM  OF  THE  BLOOD  VESSELS  OF  THE  HUMAN  SPLEEN. 

At  x  is  shown  the  direct  connection  of  terminal  arteries  with  terminal  veins  (the  existence  of^such  a  connec- 
tion has  been  questioned).  At  xx  and  xxx  are  the  free  endings  of  the  terminal  veins  in  the  pulp  and 
near  the  nodules  respectively. 

gland,  the  spleen  is  deficient  in  lymphoid  tissue  (Fig.  198).  ??The  bulk 
of  the  spleen  is  composed  of  splenic  pulp,  which  corresponds  with  the 
blood  sinus  of  the  haemolymph  glands.  Its  framework  of  reticular  tissue 
is  continuous  with  that  of  the  nodules,  and  it  contains  blood  corpuscles 
of  all  sorts,  special.phagocytic  cells  known  as  splenic  cells,  and  the  terminal 
branches  of  both  arteries  and  veins.  There  are  no  lymphatic  vessels 
within  the  spleen.  The  .capsule  and  trabecular  framework  are  highly 
developed  as  in  the  largest  lymph  glands.  The  following  features  of  the 
spleen  may  be  described  in  turn — the  blood  vessels,  the  pulp,  the  nodules, 
the  capsule  and  trabeculae,  and  finally  the  nerves. 

As  shown  in  the  diagram,  Fig.  199,  the  splenic  artery  enters  at  the 
hilus  and,  accompanied  by  veins,  its  branches  are  found  in  the  largest 
trabeculae.  When  about  0.2  mm.  in  diameter  the  arteries  leave  the  trabec- 


212  HISTOLOGY 

ulae,  in  which  the  veins  continue  further.  The  arteries,  however,  are  still 
surrounded  by  a  considerable  connective  tissue  layer,  the  outer  portion  of 
which  becomes  reticular  and  is  filled  with  the  lymphocytes  of  the  nodules. 
The  nodules  occur  near  where  the  artery  branches.  Small  arterial  twigs 
ramify  in  the  nodules,  in  the  periphery  of  which  they  anastomose  before 
passing  into  the  pulp.  When  the  main  stems  are  about  15  /z  in  diameter, 
they  lose  their  surrounding  lymphoid  layer  and  pass  into  the  pulp,  where 
they  form  brush-like  groups  of  branches  (penicilli).  These  branches  do 
not  anastomose.  For  a  short  distance  before  their  termination  the  walls 
of  the  branches  possess  ellipsoid  thickenings,  due  to  a  longitudinal  ar- 
rangement of  closely  applied  fibers  of  reticular  tissue.  These  "sheathed 

arteries"  are  6-8  /z  in  dia- 
meter, and  have  been  sup- 
posed to  regulate  the  amount 
of  blood  which  enters  the 
terminal  portion  of  the  artery, 
beyond  them.  Some  autho- 
rities state  that  this  distal 
part  connects  with  the  ter- 


FIG.   300.-CROSS    SECTION    (A)     ANO  -S.RKACE    VIEW   (B)   OK 

TERMINAL  VEINS  FROM  THE  HUMAN  SPLEEN-  aj-    an   acute  angle.      AcCOrd- 

e.,  Rod  shaped  endothelial  cells,  with  projecting  nuclei,  n  ;  r.,  . 

encircling  reticular  tissue;  1.,  leucocytes  passing  between  mcr     to     Others    SUCh     COnnCC- 

the  endothelial  cells.     (After  Weidenreich.)  f  & 

tions  are  infrequent,  and  still 

others  belief'  that  the  arteries  empty  only  into  the  reticular  tissue. 
Numerous  careful  injections  have  shown  the  readiness  with  which  the 
arterial  |jood  mingles  with  the  pulp  cells. 

The  terminal  veins  or  splenic  sinuses  begin  as  dilated  structures  (some- 
times unfortunately  called  "ampullae/7  the  latter  term  being  applied 
also  to  the  terminal  arteries).  Their  endothelial  cells  are  so  long  and 
slender  as  to  suggest  smooth  muscle  fibers,  and  like  certain  other  endothe- 
lial cells  they  are  contractile.  Their  edges  are  not  closely  approximated, 
so  that  corpuscles  may  pass  between  them  freely  (Fig.  200)  .  Around  them 
are  encircling  reticular  tissue  fibers,  and  a  continuous  basement  membrane 
has  been  described  as  stretching  across  the  intervals  between  the  endothelial 
cells.  The  existence  of  such  a  membrane  has  recently  been  denied.  The 
endothelial  cells  project  into  the  lumen  of  the  vessel,  and  their  nuclei  are 
at  the  summits  of  the  elevations.  Frequently  the  nuclei  show  one  or 
two  longitudinal  rod-like  markings,  said  to  be  due  to  folds  in  the  nuclear 
membrane  (Fig.  200,  B)  Several  terminal  veins  unite  to  form  a  pulp  vein, 
which  enters  a  trabecula  in  which  it  passes  toward  the  hilus.  The  tra- 
becular  veins  join  to  form  the  splenic  vein. 

For  further  details  regarding  the  circulation  see  Weidenreich  (Arch.  f.  mikr.  Anat., 
1901,  vol.  58,  pp.  247-376)  and  Mall  (Amer.  Journ.  Anat.,  1903,  vol.  2,  pp.  315-332). 


SPLEEN  213 

The  splenic  pulp  consists  of  a  reticular  tissue  framework  (Fig.  50, 
p.  61).  It  supports  the  terminal  arteries  and  veins,  and  in  its  meshes 
are  the  white  and  red  corpuscles  passing  between  them. 

The  pulp  appears  as  a  diffuse  mass  of  cells  infiltrated  with  red  cor- 
puscles, and  since  the  vessels  within  it  are  thin- walled  and  hard  to  follow, 
likewise  containing  corpuscles,  it  is  often  impossible  in  ordinary  sections 
to  determine  which  cells  are  inside  and  which  are  outside  of  the  vessels 
(Fig.  201).  The  nodules  are  not  sharply  separated  from  the  pulp,  so 
that  lymphocytes  are  abundant  in  their  vicinity.  These  lymphocytes 
enter  the  terminal  veins  and  thus  are  removed  from  the  spleen.  In  the 
splenic  vein  the  proportion  of  lymphocytes  to  red  corpuscles  is  said  to  be 
seventy  times  as  great  as  in  the  splenic  artery.  One  for  every  four  red 


Capsule. 


Pulp. 


Spindle-shaped 
nodule. 


Sheathed  artery. 


Central  arteries  in 
splenic  nodules. 


FIG.  201. — PART  OF  A  SECTION  OF  THE  SPLEEN  FROM  AN  ADULT  MAN.     X  15. 

corpuscles  has  been  reported  by  two  investigators,  but  later  estimates  are 
lower.  It  seems  evident  that  lymphocyte  production  is  an  important 
function  of  the  spleen.  Another  is  the  nitration  of  the  blood  passing 
through  the  pulp.  As  in  haemolymph  glands,  granular  debris  is  found, 
and  there  are  phagocytic,  pigmented,  and  eosinophilic  cells.  The  phago- 
cytes are  cells  with  large  round  nuclei  and  considerable  protoplasm.  They 
vary  in  size,  but  the  small  forms  are  most  numerous;  these  are  called  splenic 
cells.  Some  are  described  as  multinucleate.  Erythroblasts  are  not  found 
in  the  normal  adult  human  spleen;  they  occur,  however,  in  certain  blood 
diseases,  and  are  normal  in  some  adult  mammals,  as  in  the  skunk.  They 
are  abundant  in  the  spleens  of  human  embryos.  Giant  cells  are  numerous 
in  the  spleens  of  young  animals  but  are  seldom  found  in  the  human  adult. 


214 


HISTOLOGY 


They  are  described  as  megakaryocytes,  and  are  like  those  in  bone  marrow. 
The  formation  of  granular  leucocytes,  which  has  been  asserted,  presum- 
ably does  not  occur. 

The  splenic  nodules  are  quite  like  the  secondary  nodules  of  lymph 
glands.  They  consist  of  a  reticular  tissue  framework  continuous  with 
that  of  the  pulp,  but  having  coarser  meshes.  Fine  elastic  fibers  are  as- 
sociated with  it.  It  contains  lymphocytes,  and  near  the  central  arteries 


.     Surface    blackened 
by  precipitate  of 
silver. 


Nerve   branches 

for  the  arterial 

wall. 


Nerves  of  the  pulp. 


\ 


Small  nerve  _ 
bundle. 

Branches  for  the         / '/A 
arterial  wall. .'-  —  -' 
FIG.  202. — GOLGI   PREPARATION  OF  THE  SPLEEN  OF  A  MOUSE.     X  85. 
The  boundary  between  the  splenic  pulp  and  the  lymphoid  tissue  is  indicated  by  a  dotted  line. 
The  nerves  are  chiefly  in  the  wall  of  an  artery. 

germinal  centers  are  sometimes  distinct.  The  nodules  have  been  regarded 
as  varying  in  shape  from  time  to  time,  being  but  transient  accumulations 
of  lymphocytes. 

The  capsule  of  the  spleen  is  divided  into  two  layers.  The  outer  is 
the  tunica  serosa  and  the  inner,  the  tunica  albuginea.  The  serosa  con- 
sists of  the  peritoneal  mesothelium,  which  covers  the  spleen  except  at 
the  hilus,  and  of  the  underlying  connective  tissue.  The  albuginea  is  a 
dense  layer  of  connective  tissue,  containing  elastic  networks  and  smooth 
muscle  fibers.  Similar  tissue  is  found  in  the  trabeculae.  The  muscle 


SPLEEN  215 

elements  are  less  numerous  in  the  human  spleen  than  in  those  of  many 
animals.  By  contraction  they  force  blood  from  the,  pulp  and  cause  the 
circulation  to  follow  more  definite  channels.  When  they  are  paralyzed, 
the  pulp  becomes  filled  with  the  blood  corpuscles. 

The  nerves  of  the  spleen,  from  the  right  vagus  and  the  cceliac  sympa- 
thetic plexus,  are  medullated  and  non-medullated  fibers,  chiefly  the  latter. 
They  form  plexuses  around  the  blood  vessels  (Fig.  202)  and  send  fibers 
into  the  pulp.  Besides  supplying  the  muscles  of  the  vessels  and  trabeculae, 
some  of  them  are  thought  to  have  free  sensory  endings.  Lymphatic 
vessels  are  said  to  occur  in  the  capsule  and  trabeculae,  but  not  in  the  pulp 
or  nodules  of  the  spleen. 

The  spleen  is  a  large  organ,  without  obvious  subdivisions.  On  its  surface,  when 
fresh,  there  is  a  mottled  effect  due  to  areas  bounded  more  or  less  definitely  by  tra- 
beculae. Such  areas,  about  i  mm.  in  diameter,  have  been  described  by  Mall  as  "lobules," 
and  he  states  that  they  "can  easily  be  seen  on  the  surface  of  the  organ  or  in  sections." 
A  lobule,  as  he  describes  it,  has  a  central  artery,  and  its  base  is  where  the  lymphoid 
sheath  of  the  artery  terminates.  It  has  peripheral  veins,  often  three,  enclosed  in  the 
trabeculae.  A  lobule  is  composed  of  some  ten  structural  (or  histological)  units,  imper- 
fectly separated  from  one  another  by  branches  of  the  trabeculae.  Each  unit  contains  a 
central  terminal  artery  (branches  of  the  lobular  artery)  and  has  peripheral  veins 
(branches  of  those  about  the  lobule).  Apparently,  therefore,  the  lobules  shown  in  the 
diagram,  Fig.  199,  except  along  its  lower  border,  represent  groups  or  pairs  of  Mall's 
lobules.  Stohr  notes  that  "a  division  into  lobules  in  the  interior  of  the  spleen  is  im- 
possible." The  arrangement  of  lobules  at  the  periphery  suggests  an  ill-defined  cortex. 
Lobes  have  also  been  described,  corresponding  with  the  main  branches  of  the  splenic 
artery,  but  the  lobes  are  not  generally  recognized.  The  spleen  may  present  inconstant 
subdivisions,  which  sometimes  produce  detached  portions  called  accessory  spleens. 

.     THE  ENTODERMAL  TRACT. 

DEVELOPMENT  OF  THE  MOUTH  AND  PHARYNX. 

In  a  previous  section  the  early  development  of  the  fore-gut  or  pharyn- 
geal  pocket  of  entoderm  has  been  described  and  illustrated  (Figs.  27  and 
28).  This  fore-gut  of  the  young  embryo  is  to  produce  the  pharynx, 
oesophagus,  and  stomach  of  the  adult.  Its  anterior  extremity  encounters 
the  ectoderm  at  the  bottom  of  a  depression.  The  ectoderm  and  entoderm 
there  fuse  to  make  the  oral  plate  (Fig.  203),  which  becomes  thin,  ruptures, 
and  disappears.  Just  anterior  to  the  plate,  in  the  median  line,  the 
ectoderm  sends  a  gland-like  projection  toward  the  brain.  It  branches 
and  becomes  detached  from  the  oral  ectoderm,  lying  in  the  sella  turcica 
of  the  adult.  It  is  known  as  the  anterior  lobe  of  the  hypophysis,  and  will 
be  described  with  the  brain,  from  which  the  posterior  lobe  develops. 
The  ectoderm  in  front  of  the  oral  plate  forms  also  the  epithelium  of  the 
lips  and  of  the  peripheral  part  of  the  mouth,  including  the  enamel  organs, 
as  has  already  been  described.  The  salivary  glands  are  also  considered 


2l6 


HISTOLOGY 


ectodermal,  but  before  they  develop  the  oral  plate  has  disappeared  and 
the  boundary  between  ectoderm  and  entoderm  cannot  be  sharply  drawn. 
The  entoderm  of  the  mouth  and  pharynx  is  a  layer  of  epithelium  lining 
a  broad,  dorso-ventrally  flattened  cavity.     From  this  cavity,  a  succession 
of  paired  outpocke tings  grow  out  laterally  to  meet 
the  ectoderm  on  the  side  of  the  neck;  these  are 
the  pharyngeal  pouches.     They  reach  the  ectoderm 
at  the  bottom  of  furrows  or  clefts,  corresponding 
in  number  with  the  pharyngeal  pouches,  and  there 
the  two  germ  layers  fuse.     The  plates  thus  formed 


clef  ts)  . 


FIG.  203.—  DIAGRAM  SHOWING  are  comparable  with  the  oral  plate,  and  in  fishes 

THE  RELATIONS  BETWEEN  .  »•«"**        /    -n 

ECTODERM    AND    ENTO-  they  rupture   producing  the  branchial  clefts  (gill 

DERM  IN  THE  MOUTH  OF  A  * 

MAMMALIAN  EMBRYO. 
a.  1.,  and  p.  1.,  Anterior  and 

posterior    lobes     of     the  .  .    .      .  . 

hypophysis;  m.  t.,  medui-         Their  arrangement  in  a  young  dog-fish  is  shown  in  Fig. 
«Jrp.,torai  plate;  x.  and™!   204.    The  mouth,  m,  leads  into  a  cavity,  the  pharynx,  which 
opens  freely  on  the  outer  surface  of  the  fish  through  five 

8111   defts>    Z'C>      It:   als°   °PeDS  tO    the    SUrfaCC   through  the 

spiracle,  sp.,  a  structure  similar  to  the  gill  clefts,  but  an- 
terior to  them  and  having  a  more  dorsal  aperture.  In  respiration  water  is  taken  in 
through  the  mouth  and  spiracle,  and  passes  out  through  the  gill  clefts;  but  sometimes 
water  is  ejected  through  the  spiracle.  In  mammals  the  corresponding  structure  is 
counted  as  the  first  gill  cleft. 

In  mammalian  embryos  there  are  four  well-defined  pharyngeal 
pouches  on  either  side,  which  reach  the  ectoderm  at  the  bottom  of  corre- 
sponding grooves;  but  if  their  closing  plates  ever  rupture  they  are  soon 
restored,  and  permanent  openings  from  the  pharynx  on  the  side  of  the 


FIG.  204. — HEAD  OF  A  YOUNG  DOG-FISH. 
g.  c.,  Gill  cleft;  m.,  mouth;  n.,  nasal  pit;  sp.,  spiracle. 


FIG.  205. — HEAD  OF  HUMAN  EMBRYO  [OF 
10  MM.^ 

c.  s.,  cervical  sinus;  g.  c.  2.,  second  branchial 
groove;  h.,  hyoid  arch;  m.,  mouth;  md., 
mandibular  process;  n.,  nasal  pit;  sp., 
auditory  (spiracular)  groove. 


neck  are  not  found.  The  first  pouch,  corresponding  with  the  spiracle, 
connects  with  the  auditory  groove  (Fig.  205,  sp).  Around  it  the  external 
ear  develops,  so  that  its  position  is  always  evident.  The  ectodermal 
depression  which  connects  with  the  second  pouch  disappears,  except  in 
rare  cases,  where  it  forms  a  cervical  fistula.  This  is  a  pit,  or  slender  tube, 
in  the  skin  of  the  neck,  situated  primarily  between  the  hyoid  bone  and 
thyreoid  cartilage.  The  third  and  fourth  pouches  connect  with  the 


DEVELOPMENT   OF   THE   PHARYNX 


217 


i>  2,  3,  4,  the  pharyngeal  pouches. 


ectoderm  at  the  'bottom,  of  a  single  funnel-shaped  depression  known  as 
the  cervical  sinus  (Fig.  205,  c.s.).  This  also  wholly  disappears  normally, 
but  it  may  remain  as  a  cervical  fistula  low  down  on  the  neck,  and  its 
deeper -parts  may  give  rise  to  branchial  cysts.  Thus  all  the  ectodermal 
branchial  grooves  except  the  first  normally 
disappear  before  birth. 

The  pharyngeal  pouches,  or  entodermal 
portions  of  the  gill  clefts,  as  they  occur  in 
a  mammalian  embryo  are  shown  in  Fig. 
206.  The  pharynx  opens  to  the  exterior 
at  the  mouth,  mt  and  divides  posteriorly 
into  the  trachea,  tr,  and  oesophagus,  oe. 
In  the  median  dorsal  line  it  gives  rise  to 
the  anterior  lobe  of  the  hypophysis,  cut  off 
at  a.  L,  and  in  the  median  ventral  line  to 
the  thyreoid  gland,  t.  This  gland  is  a  median  structure,  entirely  sepa- 
rate from  the  pharyngeal  pouches.  It  grows  down  through  the  hind 
part  of  the  tongue,  acquiring  a  position  in  front  of  the  trachea.  Its 
branching  terminal  part  becomes  separated  from  its  outlet  by  the  ob- 
literation of  its  duct  (called  the  thy- 
reoglossal  duct).  A  blind  pit,  the 
foramen  ccecum,  permanently  re- 
tained at  the  back  of  the  tongue, 
marks  the  former  outlet  of  the  duct 
(Fig.  207,7.  c>).  Thus  the  thyreoid 
gland  is  a  detached  clump  of  ento- 
dermal tubules  in  front  of  the 
trachea. 

The  entodermal  portions  of  the 
gill  clefts  are  four  paired  lateral 
outpocketings.  The  first  (Fig.  206, 
i)  extends  to  the  auditory  groove  in 
the  ectoderm,  and  becomes  the  audi- 
tory tube  (Eustachian  tube).  The 
pharyngeal  orifice  of  this  tube  in  the 

FIG.   207. — A    MEDIAN    SECTION    THROUGH    THE       j    ij.    •        ~u  *       t?:  ./       A/\ 

PHARYNX  OF  AN  ADULT.     (After  Corning.)  adult   IS    SllOWn   in    Tig.   2C>7   (0.  ph.)  ', 

a.  „-*..  Palato-slossal  arch:  a.  T>-T>..  mlato-pharyn-    ^  Quter  end  Qf   fa  tube  expands  tO 


s.t 


form  the  tympanic  cavity  of  the  ear, 

ph.,  pharyngeal  recess;  s.t.,  sellaturcica  (which  ,         -111        r       .,1  •  i  i         *,i 

contains  the  hypophysis);  t.  L,  lingual  tonsil;    and   Will   be    further    Considered   With 
tons.,  palatine  tonsil;  t.  ph.,  pharyngeal  tonsil. 

the  sense  organs. 

The  second  pharyngeal  pouch  (Fig.  206,  2)  loses  its  connection  with  the 
ectoderm  and  becomes  a  relatively  shallow  depression  on  the  side  of  the 
pharynx.  At  a  certain  stage  it  is  in  close  relation  with  the  orifice  of  the 


2l8  HISTOLOGY 

auditory  tube,  and  it  has  been  thought  to  give  rise  to  the  pharyngeal 
recess  (fossa  of  Rosenmiiller),  but  according  to  Hammar  such  is  not  the 
case.  Instead,  it  produces  only  the  sinus  tonsillaris,  into  which  a  mound  of 
lymphoid  tissue,  the  palatine  tonsil,  later  projects  (Fig.  207,  tons.).  -Above 
the  tonsil  the  supratonsillar  fossa,  which  may  readily  be  seen  on  looking 
into  the  mouth,  is  to  be  regarded  as  a  remnant  of  the  original  second 
pouch  (Hammar,  Arch.  f.  mikr.  Anat.,  1903,  vol.  61,  pp.  404-458). 

The  lingual  and  pharyngeal  tonsils,  which  are  similar  in  structure  to  the  palatine 
tonsils,  develop  as  median  structures  with  no  relation  to  the  pharyngeal  pouches. 
Therefore  the  second  pouches  are  to  be  regarded  as  the  site  rather  than  the  source  of 
the  palatine  tonsils;  there  are  no  tonsils  in  the  second  pouches  of  the  rat  (Hammar). 

The  third  pouch  (Fig.  206,  3)  near  its  junction  with  the  ectoderm, 
sends  a  tubular  diverticulum  (th)  down  the  neck  behind  the  thyreoid 
gland;  it  continues  into  the  thorax,  lying  ventral  to 
the  arch  of  the  aorta  (as  seen  in  front  view  in  Fig. 
208).  This  diverticulum  loses  its  lumen,  becomes 
detached  from  the  pharynx,  and  unites  with  its  fellow 
on  the  opposite  side  to  form  the  thymus.  Besides 
this  elongated  structure,  each  third  pouch  produces 
an  epithelial  body,  or  nodulus  thymicus,  which  is  a 
round  clump  of  cells  detached  from  the  pouch  at  the 
FIG.  208.  upper  end  of  the  thymic  diverticulum.  Each  epithe- 

TheremdmutSl  'of'  Ig^mm  ^  body  becomes  attached  to  the  posterior  surface 
of  the  thyreoid  gland,  forming  the  inferior  pair  of 
parathyreoid  glands  (Fig.  208,  p.). 


freo°m  thgela4th     S*)          The  fourth  pouch  on  either  side  (Fig.  206,  4)  gives 

p.  1.,  pyramidal  lobe  of  .  ,     . .    .  .       .  M  _, ,  ,    ,         J , 

the  thyreoid;  ao.  rise  to  an  epithelial  body  similar  to  the  nodulus  tny- 

aorta;    v.,    vena    cava 

superior.    (After  Ver-  micus.     These  likewise  become  detached  as  parathy- 

dun.)  f  J 

reoid  glands,  and  they  constitute  the  superior  pair 
(Fig.  208,  p.  g.).  Sometimes  a  para  thyreoid  gland  degenerates  and  dis- 
appears, and  in  other  cases  one  of  them  may  become  subdivided,  but 
typically  there  are  four  in  the  adult. 

Behind  the  fourth  pouch,  on  either  side,  there  is  a  tubular  prolonga- 
tion of  the  pharynx  variously  known  as  the  postbranchial,  ultimobranch- 
ial  or  telobranchial  body.  As  the  fourth  pouch  becomes  well  formed, 
the  postbranchial  body  is  so  closely  associated  with  it  that  together  they 
form  a  Y-shaped  structure,  attached  to  the  pharynx  by  a  common  stalk 
(Fig.  206).  The  postbranchial  bodies  then  grow  toward  one  another 
across  the  front  of  the  neck,  after  the  manner  of  the  thymic  diverticula. 
Their  ventral  ends  become  detached  and  imbedded  in  the  thyreoid  gland, 
to  the  substance  of  which  they  were  formerly  believed  to  contribute. 
There  is,  however,  no  satisfactory  evidence  that  they  produce  thyreoid 
tissue,  and  they  are  generally  supposed  to  disintegrate. 


DEVELOPMENT   OF    THE   PHARYNX  2IQ 

The  first  recognition  of  the  significance  of  the  mammalian  gill  clefts  is  credited  to 
Rathke,  in  1832,  who  published  the  following  significant  conclusions  in  his  "Unter- 
suchungen  iiber  den  Kiemenapparat  der  Wirbelthiere." 

"In  all  vertebrates  without  exception,  in  the  earliest  period  of  development,  there 
are  formed  the  beginnings  of  a  branchial  apparatus.  Its  elements  vary  in  number  in 
the  different  vertebrates,  yet  in  tissue,  form,  position  and  connections  they  are  very 
similar  to  one  another,  and  are  built  upon  the  same  plan.  Their  development,  how- 
ever, proceeds  along  different  lines  in  the  various  animals.  In  some  it  is  partly  re- 
gressive, bringing  about  the  most  manifold  and  divergent  modifications  of  these 
structures,  not  merely  in  form  but  also  in  tissue,  type,  and  significance.  Yet  there 
always  remains  an  analogy  between  them;  and  through  easy  transitions,  the  forms  and 
types  pass  into  one  another  from  the  bony  fishes  even  to  man.  The  branchial  appara- 
tus is  most  highly  developed  in  fishes;  in  the  other  vertebrates  its  development  is  the 
less  complete,  the  further,  in  general,  these  vertebrates  are  removed  from  the  fishes." 

The  mammalian  gill  clefts,  although  rudimentary  as  branchial  organs, 
are  of  the  utmost  anatomical  importance.  A  single  large  artery  passes 
from  the  ventral  aorta  to  the  dorsal  aorta  between  the  successive  pouches, 
and  also  in  front  of  the  first  and  behind  the  last.  These  aortic  arches 
therefore  number  one  more  than  the  series  of  pouches;  from  them,  portions 
of  the  aorta,  carotid  and  subclavian  arteries  are  produced,  as  described 
in  works  on  embryology.  The  nerves  send  trunks  down  between  the 
pouches,  the  facial  nerve  being  between  the  first  and  second,  the  glosso- 
pharyngeus  between  the  second  and  third,  and  the  superior  laryngeal 
branch  of  the  vagus  between  the  third  and  fourth.  Thus  these  structures 
determine  the  arrangement  of  the  vessels  and  nerves. 

On  the  basis  of  comparative  studies  the  presence  of  a  fifth  pouch  in  mammals  was 
predicted,  and  the  posterior  arm  of  the  Y-shaped  outgrowth,  including  the  postbran- 
chial  body,  is  often  described  as  such.  A  branch  of  the  superior  laryngeal  nerve  is  said 
to  pass  between  the  arms  of  the  Y,  but  a  typical  branchial  relation  between  the  nerves 
and  the  fifth  pouch  has  not  as  yet  been  established.  A  "fifth  aortic  arch "  is  often  rep- 
resented as  passing  between  the  fourth  pouch  and  the  postbranchial  body,  but  it  has 
been  shown  that  this  arch  differs  from  all  the  others  in  its  order  of  development  (form- 
ing only  after  the  "sixth"  is  complete).  Whereas  the  third,  fourth,  and  last  aortic 
arches  all  produce  very  important  vessels,  the  questionable  "fifth  arch"  is  an  insignifi- 
cant plexiform  anastomosis,  which  disappears  rapidly.  Small  vessels,  however,  are 
always  to  be  found  near  the  postbranchial  body  in  rabbit,  pig  and  human  embryos 
measuring  5-10  mm.  The  most  convincing  evidence  of  the  presence  of  a  fifth  pouch  is 
an  actual  contact  with  the  ectoderm,  posterior  to  the  fourth  pouch;  this  was  recorded 
by  Hammar  in  a  5-mm.  embryo,  but  the  contact  on  either  side  took  place  in  only  one 
12  (i  section.  Grosser  states  that  a  closing  membrane  "is  perhaps  not  always  formed, 
and  is  at  all  events  very  transitory"  (Human  Embryology,  ed.  by  Keibel  and  Mall, 
1912,  vol.  2).  There  are  as  yet  very  few  observations  to  show  that  it  ever  occurs  in 
mammalian  embryos.  The  existence  of  a  sixth  pouch  has  been  asserted  on  the  basis 
of  slight  elevations  which  are  perhaps  inconstant. 

TONSILS. 

The  palatine  tonsils  are  two  rounded  masses  of  lymphoid  tissue,  one 
on  either  side  of  the  throat,  between  the  arches  of  the  palate  (Fig.  207.) 


22O  HISTOLOGY 

Frequently  they  have  been  called  amygdala  (almonds),  but  the  older 
Latin  term  for  them  is  tonsilla  (a  stake  to  which  boats  are  tied).  They 
are  covered  by  the  mucous  membrane  or  tunica  mucosa,  which  throughout 
the  digestive  tract  consists  of  several  layers.  The  soft  moist  entodermal 
epithelium  rests  on  a  connective  or  reticular  tissue  layer,  the  tunica  propria. 
A  structureless  basement  membrane,  the  membrana  propria,  is  often  pres- 
ent immediately  beneath  the  epithelium.  The  epithelium,  membrana 
propria,  and  tunica  propria  together  form  the  mucous  membrane,  which 
in  dissection  would  be  stripped  off  as  a  single  structure.  Beneath  it,  and 
sometimes  not  clearly  separable  from  the  tunica  propria,  is  the  submucous 


Jf 

FIG.  209. — VERTICAL  SECTION  OF  A  HUMAN  PALATINE  TONSIL. 

a,  Stratified  epithelium;  b,  basement  membrane;  c,  tunica  propria;  d,  trabeculae;  e,  diffuse  lymphoid 
tissue;  f,  nodules;  h,  capsule;  i,  mucous  glands;  k,  striated  muscle;  1,  blood  vessel;  q,  pits.  (From 
Radasch.) 

layer,  or  tela  submucosa.  It  is  a  vascular  connective  tissue,  by  which  the 
mucous  membrane  is  attached  to  underlying  muscles  or  bones.  All  the 
layers  named  are  involved  in  the  tonsils  which,  however,  are  essentially 
lymphoid  accumulations  in  the  tunica  propria. 

The  epithelium  of  the  palatine  tonsils  is  a  stratified  epithelium  of 
many  layers,  with  flattened  cells  on  its  smooth  free  surface,  and  columnar 
cells  beneath.  Its  attached  surface  is  invaded  by  connective  tissue  ele- 
vations or  papillae,  so  that  it  appears  wavy  in  sections  (Fig.  209).  The 
stratified  epithelium  lines  from  ten  to  twenty  almost  macroscopic  depres- 
sions, called  tonsillar  pits  or  fossulce  (crypts).  These  are  irregularly  tub- 
ular and  sometimes  branched.  Many  lymphocytes  penetrate  between 
the  epithelial  cells  and  escape  from  the  free  surface  into  the  saliva,  be- 
coming "salivary  corpuscles."  In  places  the  tonsillar  epithelium  is  so 
full  of  lymphocytes  as  to  appear  disintegrated,  a  condition  which  was 


first  c 


TONSILS 


221 


rst  described  by  Stohr^(Biol.  Centrabl.,  1882,  vol.  2).     It  occurs  also  in 
the  epithelium  of  the  lingual  tonsil  as  seen  in  Fig.  211.      In  the  reticular 


Pit. 


Epithelium." 
Tunica  propria. 


Fibrous  sheath.  " 


Germinal  center.  Epithelium  and  pit  containing  lymphocytes. 

FIG.  210. — VERTICAL  SECTION  THROUGH  A  PIT  IN  THE  LINGUAL  TONSIL  OF  AN  ADULT  MAN.     X  260 


Emigrated  ^ 

lymphocytes.  & 


Emigrating  lymphocytes. 


•*•* 


Fragments  of  epithelium. 


Stratified  < 
epithelium 


Lymphoid  tissue 

of  the  tunica 

propria. 


• 


^MtetVMT* /"•*•-- 

$frt. 

^^  :  &'  $  "^r^^ 
§L~4»/-  ©     ^-/IL^T'X— -v-^-,?,- 


I 

*1^^ 

P^*F^f 
«* 


^^£^ 


FIG.  211. — FROM  A  THIN  SECTION  OF  A  LINGUAL  TONSIL  OF  AN  ADULT  MAN.     X  420. 
On  the  left  the  epithelium  is  free  from  lymphocytes,  on  the  right  many  lymphocytes  are  wandering  through. 

tissue  of  the  tunica  propria,  especially  around  the  pits,  there  are  many 
lymph  nodules,  some  of  which  are  well  defined,  with  germinative  centers, 


222  HISTOLOGY 

but  many  others  are  fused  in  indefinite  masses.  The  lymphoid  tissue 
constitutes  the  bulk  of  the  tonsil. 

The  submucous  layer  forms  a  capsule  for  the  organ,  into  which  it 
sends  trabecular  prolongations.  It  contains  many  blood  and  lymphatic 
vessels,  together  with  branches  of  the  glossopharyngeal  nerve  and 
spheno-palatine  ganglion  which  supply  the  tonsil.  It  contains  also  the 
secreting  portions  of  small  mucous  glands,  some  of  which  empty  into  the 
pits,  but  most  of  their  ducts  terminate  in  the  mucous  membrane  sur- 
rounding the  tonsil.  They  resemble  other  mucous  glands  of  the  mouth 
which  will  be  described  presently.  Beyond  the  submucosa  is  striated 
muscle,  belonging  to  the  arches  of  the  palate  and  to  the  superior  constrictor 
of  the  pharynx;  striated  muscle  fibers  are  therefore  readily  included  in 
sections  of  the  tonsil. 

The  pharyngeal  tonsil  is  an  accumulation  of  lymphoid  tissue  on  the 
median  dorsal  wall  of  the  pharynx,  between  the  openings  of  the  auditory 
tubes  (Fig.  207).  In  childhood  it  is  liable  to  become  irregularly  enlarged 
so  as  to  obstruct  the  inner  nasal  openings,  thus  forming  the  " adenoids" 
of  clinicians.  It  is  covered  with  stratified  epithelium,  which  is  ciliated 
in  embryonic  life;  and  in  the  adult,  cilia  may  be  found  upon  the  epithelium 
within  the  pits.  The  pits  and  lymphoid  tissue  are  quite  like  those  of 
the  palatine  tonsils. 

The  lingual  tonsil  is  an  aggregation  of  pits  surrounded  by  lymphoid 
tissue  (Fig.  210).  It  is  found  in  the  back  part  of  the  tongue  (Figs.  207  and 
220),  the  surface  of  which  is  very  different  in  texture  from  the  front  part, 
presenting  low  mounds  with  central  depressions.  Each  depression  is  the 
outlet  of  a  pit.  Lymphocytes  pass  through  the  epithelium  (Fig.  211) 
and  become  salivary  corpuscles,  which  are  said  to  produce  substances 
protecting  the  tissue  from  bacterial  invasion. 

THYMUS. 

The  thymus  (Gr.  tfv/xos,  thymus)  arises  from  the  two  tubular  prolonga- 
tions of  the  third  pharyngeal  pouches,  which  meet  in  the  median  line  as 
shown  in  Fig.  208,  and  become  bound  together  by  their  connective  tissue 
coverings.  The  lumen  is  lost,  and  the  cells  proliferate.  They  form  a 
broad,  flat,  bilobed  mass  with  a  tapering  prolongation  up  either  side  of 
the  neck.  The  bulk  of  the  organ  is  in  the  thorax,  beneath  the  upper  part 
of  the  sternum.  At  birth  it  weighs  generally  between  5  and  15  grams 
(about  half  an  ounce),  and  is  relatively  a  large  organ.  Haller  (1761) 
described  it  in  older  embryos  as  "a  huge  gland,  scarcely  smaller  than  the 
kidney;  but  in  the  adult  it  is  diminished,  and  having  become  constricted, 
dried  up  and  much  harder,  it  is  almost  buried  in  the  surrounding  fat." 
Meek  el  found  ordinarily  no  trace  of  it  at  twelve  years,  and  according  to 


THYMUS 


223 


Hewson  it  gradually  wastes  until  the  child  has  reached  between  its  tenth 
and  twelfth  year,  when  ordinarily  it  is  perfectly  effaced,  leaving  only  liga- 
mentous  remains.  These  older  observations  have  been  generally  ac- 
cepted, and  the  persistence  of  the  thymus  in  the  adult  is  regarded  as  of 


Thymic 
corpuscles. 


Connective  tissue. 


Transverse  section 
of  blood  vessel. 


-H    Medullary  cord. 


Cortex. 


Medulla.  . 


Blood  vessel. 

Thymic 
corpuscle.  »».'., 


FIG.  212. — FROM  A  CROSS  SECTION  OF  THE  THYMUS  OF  A  CHILD,  ONE  YEAR  AND  NINE  MONTHS  OLD.     X  21. 

considerable  pathological  importance.  According  to  Waldeyer  and  Ham- 
mar,  however,  it  persists  for  a  much  longer  time.  It  increases  in  size 
and  weight  for  some  years  after  birth,  probably  until  puberty,  and  then 
slowly  atrophies.  At  fifteen  years  it  is  said  to  weigh  40-50  grams.  It  is. 
considered  an  active  organ 
even  to  the  fortieth  year, 
losing  its  functions  with 
beginning  old  age  (50-60 
years).  The  duration  of 
the  thymus  has  apparently 
been  underestimated.  (See 
Hammar.  Arch.  f.  Anat.  u. 
Entw.,  1906,  Suppl.-Bd.  pp., 
91-182;  Anat.  Anz.,  1905, 
vol.  27,  pp.  23-89;  and  for 
development,  Anat.  Hefte, 
Abth.  i,  1911,  vol.  43,  pp. 
203-242). 

The  thymus  is  subdivi- 
ded   by    connective    tissue 

Invert   into    Jnhf"i    from   A    to    FlG-  2I3- — PART  OF  A  SECTION  OF  THE  THYMUS  FROM  A  HUMAN 
J  EMBRYO  OF  FIVE'  MONTHS.     X  50. 

ii    mm.   in  diameter,    and 

these  are  similarly  subdivided  into  lobules  of  about  i  cu.  mm.  each.  All 
the  lobules  in  the  right  and  left  halves  of  the  thymus,  respectively,  are 
attached  to  a  cord  of  medullary  substance,  1-3  mm.  in  diameter,  as  may 
be  seen  if  the  gland  is  pulled  apart.  This  axial  structure  suggests  the 


Tangential  sections  of  lobules. 


224  HISTOLOGY 

original  diver ticulum.  Each  lobule  consists  of  a  pale  medulla,  extend- 
ing from  the  cord,  and  a  darker  peripheral  cortex  (Figs.-  212  and  213). 
The  entire  structure  somewhat  resembles  a  lymph  gland,  from  which, 
however,  germinal  centers  are  absent.  It  might  be  inferred  that  lym- 
phoid  tissue  had  developed  'in  the  mesenchyma  surrounding  the  diver- 
ticulum,  in  the  same  way  that  such  tissue  forms  about  the  tonsillar 
pits,  but  careful  study  has  shown  that  the  thymus  is  largely  of  ento- 
dermal  origin.  Whether  the  cells  of  its  cortex,  which  closely  resemble 
lymphocytes,  are  true  lymphocytes  or  "  deceptively  similar  epithelial 
cells"  has  not  been  determined. 

Vein. 
Connective  tissue. 


Thymic  corpuscle. 


\ 


Entering        Medullary 
leucocytes.       substance.  \ 

Cortical 
substance. 
FIG.  214. — PART  OF  A  SECTION  OF  THE  THYMUS  OF  A  CHILD  AT  BIRTH.     X  50. 

According  to  Bell  (Amer.  Journ.  Anat.,  1905,  vol.  5,  pp.  29-62)  the  thymus  is  at 
first  a  compact  mass  of  entodermal  cells.  By  vacuolization  the  cells  form  a  reticulum, 
and  certain  of  them  become  lymphocytes.  The  lymphocytes  pass  into  the  cortex 
where  they  are  most  abundant,  and  enter  the  vessels.  The  lymphoid  transformation 
of  the  thymus  "is  noticeable  in  pigs  of  3.5  cm.  and  is  well  advanced  at  4.5  cm.'  Thus 
lymphocytes  appear  in  the  thymus  at  about  the  time  that  lymph  glands  develop. 
The  first  indication  of  lymph  glands  was  found  by  Miss  Sabin  in  pig  embryos  of  3  cm. 

That  the  thymus  cells  are  lymphocytes,  however,  is  denied  by  Stohr,  who  regards 
the  cortex  as  composed  of  a  network  of  stellate  epithelial  cells,  containing  in  its  meshes 


THYMUS 


225 


small  round  epithelial  cells  deceptively  similar  to  lymphocytes.  Of  true  leucocytes 
in  the  thymus  he  says,  "In  the  places  where  the  medulla  is  directly  in  contact  with  the 
surrounding  connective  tissue — and  such  places  become  constantly  larger  and  more 
numerous  as  the  organ  grows — many  leucocytes  wander  into  the  medulla;  they  lie 
in  the  connective  tissue  surrounding  the  medulla  but  not  in  that  around  the  cortex 
(Fig.  214).'*  He  considers  that  the  cortex  with  its  many  mitotic  figures  represents  a 
zone  of  production,  and  the  medulla,  a  zone  of  growth  and  degeneration  (Anat.  Hefte, 
Abth.  i,  1906,  vol.  31,  pp.  409-457).  Hammar  (1905,  loc.  cit.)  is  unable  to  determine 
the  source  of  the  "thymus  lymphocytes,"  but  is  confident  that  the  reticulum  is  of 
epithelial  origin.  He  finds  that  in  birds  this  reticulum  produces  cells  resembling 
striated  muscle  fibers,  and  these  "myoid  cells"  he  considers  to  be  entodermal.  In 
his  later  work  (1911,  loc.  cit.}  he  states  that  the  lymphocytes  enter  the  thymus  chiefly 
from  the  thymic  blood  vessels. 

Not  only  lymphocytes,  but  other  leucocytes,  eosinophilic  cells,  and 
multinuclear  giant  cells  have  been  found  in  the  medulla.  Erythroblasts 
are  said  to  occur  in  its  outer  portion  and  in  the  cortex.  The  thymus 


Degenerated  epithelial  cells- 


Flat  epithelial  cells. 
Degenerated  nucleus. 


FIG.  215. — THYMIC  CORPUSCLES,  IN  SECTION,  FROM  A  MAN  TWENTY-THREE  YEARS  OLD.     X  360. 

therefore  is  sometimes  considered  a  blood-forming  organ.  Sometimes 
the  medulla  contains  cysts,  which  may  be  lined  in  part  with  typical 
ciliated  cells.  The  most  characteristic  structures  in  the  thymus  are  the 
thymic  corpuscles  (Hassall's  corpuscles)  which  are  found  exclusively  in 
the  medulla.  They  are  rounded  bodies,  at  first  few  in  number  and 
small  (12-20  /*  in  diameter),  but  they  increase  rapidly  in  size  (to  a  diameter 
of  1 80  /*)  and  new  ones  are  constantly  forming.  They  are  said  to  be 
present  at  about  the  fifth  month,  and  at  birth  they  are  numerous,  varying 
in  size  as  shown  in  Fig.  215.  To  produce  them,  the  nucleus  and  pro- 
toplasm of  an  entodermal  reticular  tissue  cell  enlarge,  and  the  nucleus 
loses  its  staining  capacity  by  changes  in  its  chromatin.  A  layer  of 
deeply  staining  hyaline  substance  develops  in  the  protoplasm.  This  in- 
creases until  it  fills  the  entire  cell,  often  being  arranged  in  concentric 
layers,  and  the  nucleus  becomes  obliterated.  Neighboring  cells  are  con- 
centrically compressed  by  the  enlargement  of  this  structure,  and  by  hyaline 
15 


226  HISTOLOGY 

transformation  they  may  become  a  part  of  the  corpuscle.  The  larger 
corpuscles  are  due  to  a  fusion  of  smaller  ones,  or  to  hyaline  changes  occur- 
ring simultaneously  in  a  group  of  cells.  The  central  portion  of  a  corpuscle 
may  become  calcified.  Sometimes  it  is  vacuolated,  containing  fat.  The 
hyaline  substance  may  respond  to  mucous  stains,  but  generally  it  does  not; 
it  has  been  considered  similar  to  the  'colloid'  of  the  thyreoid  gland. 
Leucocytes  are  said  to  become  imbedded  in.  the  corpuscles,  or  to  enter 
them  and  assist  in  their  disintegration.  Thymic  corpuscles  have  been 
regarded  not  only  as  degenerative  products  of  the  entodermal  epithelium 
but  also  as  concentric  connective  tissue  masses,  and  as  blood  vessels 
with  thickened  walls  and  obliterated  cavities.  Injections  show  that 
they  are  not  connected  with  the  blood  vessels.  Although  they  have  recently 
been  described  as  active  constituents  of  the  thymus,  they  are  generally 
regarded  as  degenerations. 

The  arteries  of  the  thymus  enter  it  along  the  medullary  strand,  and 
extend  between  the  cortex  and  medulla,  sending  branches  into  both  but 
chiefly  into  the  cortex.  The  cortical  branches  empty  into  veins  between 
the  lobules;  the  others  into  veins  within  the  medulla.  There  are  many 
interlobular  lymphatic  vessels,  beginning  close  to  the  surface  of  the  gland 
substance,  and  accompanying  the  blood  vessels.  There  is  nothing  in  the 
thymus  to  correspond  with  a  lymph  sinus.  The  nerves,  chiefly  sympa- 
thetic fibers,  with  some  from  the  vagus,  terminate  along  the  vessels;  a 
very  few  have  free  endings  in  the  medulla. 

THYREOID  GLAND. 

The  thyreoid  (i.e.,  shield-shaped)  gland  is  a  median,  entodermal  down- 
growth  from  the  tongue;  its  thyreoglossal  duct  becomes  obliterated, 
leaving  the  foramen  caecum  to  mark  its  former  outlet.  The  downgrowth 
is  joined  by  cells  from  the  postbranchial  bodies,  which  fuse  with  it. 
This  entire  structure  comes  to  lie  beside  and  in  front  of  the  upper  part  of 
the  trachea.  It  consists  of  two  lateral  lobes,  each  about  two  inches  long 
and  an  inch  wide,  connected  by  an  isthmus,  about  half  an  inch  wide,  which 
crosses  the  median  line  ventral  to  the  second  and  third  tracheal  rings. 
An  unpaired  pyramidal  lobe  extends  from  the  isthmus  or  adjacent  part  of 
the  lateral  lobe  toward  the  tongue  (Fig.  208).  Irregular  detached  por- 
tions of  the  gland,  such  as  occur  especially  along  the  course  of  the  thyreo- 
glossal duct,  are  called  accessory  thyreoid  glands. 

The  proliferating  mass  of  entodermal  cells  forms  at  first  a  network  of 
solid  cords.  This  becomes  separated  into  small  masses,  within  each  of 
which  a  lumen  may  appear.  The  lumen  enlarges  and  becomes  spheroidal ; 
the  entodermal  cells  which  surround  it  form  a  simple  epithelium,  either 
columnar,  cuboidal,  or  flat.  Flat  cells  are  said  to  occur  especially  in  old 


THYREOID    GLAND 


227 


age;  usually  the  cells  are  low  columnar  or  cuboidal.  The  mature 
thyreoid  gland  consists,  therefore,  of  rounded,  closed  spaces,  or  follicles, 
bounded  by  a  simple  entodermal  epithelium  (Fig.  216).  The  follicles 
vary  greatly  in  diameter.  Generally  they  are  rounded,  but  sometimes 
they  are  elongated,  and  occasionally  they  branch  or  communicate  with  one 
another.  Among  them  are  cords  or  clumps  of  cells  which  have  not 
acquired  a  lumen. 

Within  the  follicles,  and  forming  the  most  conspicuous  feature  of  the 
thyreoid  gland  in  ordinary  sections,  is  a  hyaline  material  which  stains 


Flat  epithelium. 


Blood       '  ^     ' 
Connective  tissue.        vessels. 


Cuboidal 
epithelium. 


Artery  with 
two  thickenings. 


Colloid  with  drops 
of  mucus. 


Oblique  section  of  a  follicle. 


FIG.  216. — SECTION  OF  A  LOBULE  OF  THE  THYREOID  GLAND  FRQM  AN  ADULT  MAN.     X  220. 

deeply  with  eosine  and  is  named  'colloid.'  The  hyaline  material  in  the 
thymic  corpuscles,  the  hypophysis,  and  in  the  coagulum  in  the  cervical 
blood  and  lymphatic  vessels,  has  also  been  designated  colloid.  In  sections 
of  the  thyreoid  gland  it  usually  does  not  fill  the  follicle  but  has  contracted, 
producing  a  spiny  border.  Granules,  vacuoles  and  droplets  of  mucus,  de- 
tached cells,  leucocytes,  and  crystalloid  bodies  may  be  found  in  it.  It  is  a 
product  of  the  epithelial  cells,  in  the  protoplasm  of  which  similar  material 
has  been  detected.  It  has  been  said  that  it  is  transferred  to  the  blood  and 
lymphatic  vessels,  passing  out  between  the  epithelial  cells. 

As  has  been  learned  by  experiment,  the  thyreoid  gland  produces  an 
internal  secretion  which  is  essential  for  the  normal  growth  and  development 
of  the  body.  It  is,  however,  not  known  whether  this  secretion  leaves  the 
basal  or  free  surface  of  the  thyreoid  epithelium,  and  its  relation  to  the 


228 


HISTOLOGY 


colloid  material  is  not  clear.  The  finding  of  two  sorts  of  thyreoid  cells, 
one  of  which  produces  colloid,  and  the  other  does  not,  lacks  confirmation. 
The  cells  may  exhibit  refractive,  secretory  granules,  which  are  larger  and 
coarser  toward  the  free  surface.  Eosinophilic  granules  have  been  re- 
ported, and  in  certain  animals  other  granules  of  fatty  nature  have  been 
found,  especially  near  the  basal  surface.  Since  the  terminal  bars  are  said 
to  be  deficient  at  the  angles  where  the  epithelial  cells  meet,  an  opportunity 
is  afforded  for  the  contents  of  the  follicles  to  pass  out  between  the  epithelial 
cells  to  the  vascular  tunica  propria. 

The  thyreoid  follicles  are  surrounded  by  loose  elastic  connective  tissue, 
said  to  be  reticular  near  the  follicles,  which  contains  very  many  blood  and 
lymphatic  vessels  in  close  relation  with  the  epithelium.  Denser  connective 
tissue  forms  a  capsule  and  lobular  partitions.  It  contains  small  arteries, 
the  media  and  intima  of  which  are  said  normally  to  present  local  thicken- 
ings (Fig.  216).  The  nerves  from  the  cervical  sympathetic  ganglia  form 
perivascular  plexuses,  and  pass  to  the  follicles. 

PARATHYREOID  GLANDS. 

It  is  generally  stated  that  there  are  four  parathyreoid  glands  in  man, 
the  anterior  or  upper  pair  being  derived  from  the  fourth  pharyngeal 


W  /«&    • 


VI   k« 

^fe 


»  *  '-5*-. 

•-  e  ®  &    * 

®*  s*  ,®.o« 

fr'£jP&M. « 

ttii^t^t*^ 


'^-^1 

a®D^ 


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© 


FIG.  217. — SECTION  OF  A  HUMAN  PARATHYREOID  GLAND.     (Huber.) 

pouches,  and  the  posterior  or  lower  pair  from  the  third  (Fig.  208).  They 
are  therefore  entodermal  structures.  In  the  adult  they  are  round  or  oval 
bodies,  said  to  measure  from  3  to  13  mm.,  found  on  the  dorsal  or  tracheal 
surface  of  the  thyreoid  gland.  They  may  be  imbedded  in  its  capsule  or 
attached  to  it  by  pedicles.  Sometimes  they  (the  lower  pair?)  are  found 
in  the  thymus.  The  parathyreoid  glands  may  be  lacking  on  one  side, 
where  in  other  cases  as  many  as  four  have  been  recorded;  they  may  atrophy 


PARATHYREOID    GLANDS 


229 


=, c.t. 


and  disappear,  or  increase  in  number  by  subdivision.  Both  pairs  possess 
a  similar  structure  unlike  that  of  either  the  thyreoid  gland  or  the  thymus, 
but  resembling  the  corresponding  epithelial  bodies  of  the  lower  vetebrates. 
They  consist  of  masses  and  cords  of  polygonal,  entodermal  cells  contain- 
ing round  nuclei  with  networks  of  chromatin.  The  protoplasm  is  pale, 
"almost  homogeneous"  or  "slightly  granular,"  sometimes  containing 
vacuoles.  Cell  membranes  are  not  prominent.  Between  these  cells 
and  the  large  thin- walled  blood  vessels  which  pass  among  them  (Fig.  217), 
there  is  only  a  very  small  amount  of  connective  tissue.  A  capsule  sur- 
rounds the  entire  structure.  The  blood  vessels  are  branches  of  those 
which  supply  the  thyreoid  gland.  Little  is  known  of  the  lymphatics  or 
nerves. 

GLOMUS  CAROTICUM. 

The  glomus  caroticum  (carotid  gland)  is  largely  a  knot  of  blood  vessels 
at  the  bifurcation  of  the  common  carotid  artery.  It  is  a  reddish  body 
"5-7  mm.  long,  2.5-4 
mm.  broad,  and  1.5  mm. 
thick."  Between  its 
thin-walled,  dilated 
capillaries  there  are 
strands  of  polygonal 
chromarnne  cells,  which 
are  prone  to  disintegrate 
(Fig.  218).  Many  nerve 
fibers,  both  medullated 
and  non-medullated, 
enter  the  glomus,  and  a 
few  multipolar  ganglion 
cells  are  associated  with 
them.  Since  the  nature 
of  the  glomus  caroticum 
is  undetermined,  the 
three  views  regarding  it  MAN-  (After 

i  .  •  j      b.v.,  Blood  vessels;  e.v.,  efferent  vein;  tr.,  trabecula;  c.t.,  connective 

may    be    mentioned.  tissue  septum. 

First,  it  has  been  consid- 
ered as  derived  from  the  third  pharyngeal  pouch.  Since  it  has  recently 
been  asserted  that  the  "carotid  gland"  of  Echidna  comes  from  the 
second  pouch,  the  non-entodermal  origin  of  the  human  glomus  is  per- 
haps not  beyond  question.  Second,  it  has  been  considered  ganglionic'or 
paraganglionic  in  nature,  so  that  it  is  classed  with  nervous  structures, 
and  this  opinion  is  probably  correct.  Third,  it  is  considered  essentially 
a  vascular  formation,  containing  strands  of  modified  mesenchymal  cells. 


FIG.  218. — SECTION  OF  A   PART  OF  THE   GLOMUS   CAROTICUM  OF 


230 


HISTOLOGY 


DEVELOPMENT  AND  STRUCTURE  OF  THE  TONGUE. 

The  tongue  consists  of  two  parts,  an  anterior  and  a  posterior,  which 
differ  in  origin  and  adult  structure.     Separating  the  branchial  clefts  from 

one  another  there  are  columns 
of  tissue  known  as  branchial 
arches.  They  come  together  in 
the  median  ventral  line  to  form 
the  floor  of  the  mouth  (Fig. 
219).  In  this  figure  the  upper 
jaw  and  roof  of  the  pharynx 
have  been  cut  away;  the  bran- 
chial clefts  are  seen  as  dark  de- 
pressions bounded  laterally  by 
thin  plates.  The  first  branchial 
arch  (i)  is  between  the  oral 
and  auditory  clefts.  In  the 
median  ventral  line  an  eleva- 
tion (tuberculum  impar)  arises 

ver  the 
fourth  arch.     (From  McMurrich,  after  His.) 


FIG.  219. — FLOOR  OF  THE   PHARYNX  OF   A  IO-MM.  HU- 
MAN EMBRYO. 

I-IV.  Branchial  arches;  t1,  anterior  part  of  the  tongue; 
ts,  second  arch,  joining  the  posterior   part   of  the 
tongue    toward     the     median    line.     The    thyreoid 
gland    is    dotted.     The    epiglottis  extends  over  the 
M 


between    this    arch    and    the 
second;  it  becomes  continuous 

with  a  larger  elevated  portion  of  the  mandibular  arch  to  form  the  anterior 
part  of  the  tongue  (t1).  The  second  and  third  arches  unite  toward  the 
median  ventral  line  and  there  produce  the 
posterior  part  of  the  tongue  (t2).  Between 
the  anterior  and  posterior  parts  is  the  opening 
of  the  thyreoglossal  duct,  later  the  foramen 
caecum.  The  epiglottis  is  an  elevated  part 
of  the  third  arch  separated  from  the  poste- 
rior part  of  the  tongue  by  a  curved  groove. 
In  the  adult  (Fig.  220)  the  dor  sum  of  the 
anterior  part  of  the  tongue  is  roughened  with 
elevations  or  papilla.  These  are  chiefly  the 
slender  filiform  papilla  and  conical  papilla; 
but  knob-like  forms,  the  fungiform  papilla, 
are  scattered  among  them  over  the  entire 
surface,  and  in  life  they  can  be  easily  distin- 
guished owing  to  their  red  color.  Near  the 
junction  of  the  anterior  and  posterior  parts  of 
the  tongue  there  is  a  V-shaped  row  of  larger 
papillae,  generally  six  to  twelve  in  number, 
called  vallate  papilla.  Their  name  refers  to  the  deep  narrow  depression 
which  encircles  them.  Behind  the  apex  of  the  V,  which  is  directed 


f.c 


FIG.  220. — THE  UPPER  SURFACE  OF 
THE  ADULT  TONGUE. 

c.,  Conical  papillae;  ep.,  epiglottis;  f., 
foliate  papillae;  f.  c.,  foramen 
caecum;  f.f.,  position  of  the  fili- 
form and  fungiform  papillae;  1., 
lenticular  papillae;  1.  t.,  lingual 
tonsil;  p.  t.,  palatine  tonsil;  v., 
vallate  papillae. 


TONGUE 


231 


Primary 
papilla. 

\ 


toward  the  throat,  is  the  foramen  caecum.  On  either  side  of  the  tongue, 
as  indicated  in  the  figure,  there  are  from  three  to  eight  parallel  vertical 
folds  (2-5  mm.  long)  occurring  close  together;  these  are  the  foliate 
papilla.  In  the  foliate  and  vallate  papillae  the  organs  of  taste  are  most 
numerous.  The  under  surface  of  the  tongue  is  free  from  epithelial 
papillae;  its  mucosa  resembles  that  which  lines  the  mouth.  The  posterior 
part  of  the  tongue  has  a  nodular  surface  covered  with  soft  epithelium 
and  contains  the  lingual  tonsil,  which  has  already  been  described.  Later- 
ally it  presents  fold-like  elevations  called  lenticular  papilla. 

Filiform  papillae  (Fig.  221)  are  slender  cornified  epithelial  projections, 
composed  of  pointed  cells  which  are  described  as  stacked  like  super- 
imposed hollow  cones.  The  Cells  ^_  a^_.  Filiform  process. 
have  undergone  a  horny  hyaline 
degeneration.  These  projec- 
tions are  arranged  in  clumps 
which  rest  upon  a  group  of  from 
five  to  twenty  connective  tissue 
elevations,  or  secondary  papillae ; 
and  these  in  turn  are  at  the 
summit  of  a  cylindrical  or  coni- 
cal primary  papilla,  composed 
of  vascular  connective  tissue 
with  numerous  elastic  fibers. 
These  primary  papillae  form  the 
basal  portions  of  the  filiform 
papillae.  They  are  well  shown 
in  Fig.  222,  along  with  the  secondary  papillae,  but  the  cornified  processes 
of  the  thick  epithelium  above  them  have  undergone  post-mortem  disin- 
tegration. Most  of  the  papillae  of  the  tongue  are  of  the  filiform  type. 

Fungiform  papillae  (Fig.  222)  are  rounded  elevations  with  a  somewhat 
constricted  base,  varying  in  height  from  0.5  to  1.5  mm.  In  life  they  are 
red,  since  their  epithelium  is  not  cornified  and  transmits  the  color  of  the 
blood  beneath.  They  contain  a  primary  connective  tissue  papilla,  with 
but  few  elastic  fibers,  beset  on  all  sides  with  secondary  papillae. 

The  vallate  papillae  resemble  broad  fungiform  papillae.  They  are 
from  i  to  3  mm.  broad  and  i  to  1.5  mm.  tall,  each  being  surrounded  by  a 
deep  groove  (Fig.  223).  Their  connective  tissue  often  contains  longi- 
tudinal, oblique,  or  encircling  smooth  muscle  fibers,  the  last  named  being 
found  near  the  lateral  walls.  Secondary  papillae  are  confined  to  the  upper 
wall.  Occasionally  the  epithelium  sends  branched  prolongations  into  the 
underlying  tissue.  These  may  become  detached  from  the  surface  and 
appear  as  concentric  bulb-like  bodies  such  as  are  generally  known  as 
"epithelial  pearls."  There  are  also  branched  serous  glands  which  grow 


Fascia  lingus 


Muscle. 


Fat  cells. 

FIG.    221. — PROM    A   LONGITUDINAL    SECTION   OF    THE 
DORSUM  OF  A  HUMAN  TONGUE.     X  12. 


232 


HISTOLOGY 


down  from  the  epithelium,  having  ducts  which  open  into  the  deep  grooves 
(Fig.  223).  The  foliate  papillae  are  parallel  folds  of  mucous  membrane, 
in  the  epithelium  of  which  there  are  many  taste  buds.  These  structures, 
which  occur  also  in  the  lateral  walls  of  the  vallate  papillae  (Fig.  223), 
will  be  described  with  the  nerves  of  the  tongue. 

The  tunica  propria  of  the  mucous  membrane  is  a  loose  connective 
tissue  layer  containing  fat.  It  is  not  sharply  separated  from  the  denser 
submucosa.  At  the  tip  of  the  tongue,  or  apex  linguce,  and  over  the 
dorsum,  the  submucosa  is  particularly  firm  and  thick,  forming  the 
fascia  lingua.  Three  sorts  of  glands  branch  in  the  submucosa  and 


Secondary 
papillae  of  a     .c.-- 
fungiform 
papilla. 


Primary  papilla.  — 


Oblique  section 

of  a  filiform 

papilla. 


Cornified  epithelium. 


Secondary 

papillae  of  a 
filiform 
papilla. 


Primary 
papillae. 


Nerve,— 
Vein.  —%* 


Artery. 


Pat.' 


Fascia  linguae. 


Striated  mus- 
cle fibers. 


FIG.  222. — FROM  A  LONGITUDINAL  SECTION  OF  THE  HUMAN  TONGUE.     X  25. 
x,  Epithelium  showing  post-mortem  disintegration. 

may  extend  into  the  superficial  part  of  the  muscle  layer.  These  are 
the  serous  glands  found  near  the  vallate  and  foliate  papillae;  mucous 
glands  occurring  at  the  root  of  the  tongue,  along  its  borders,  and  in 
an  area  in  front  of  the  median  vallate  papilla;  and  the  two  mixed 
anterior  lingual  glands,  from  half  an  inch  to  an  inch  long,  each  of  which 
empties  by  five  or  six  ducts  on  the  under  surface  of  the  apex.  The 
structure  of  these  types  of  glands  will  be  described  in  the  section  on 
oral  glands. 

The  muscular  layer  consists  of  interwoven  bundles  of  striated  fibers 
which  are  inserted  into  the  submucosa  or  into  the  intermuscular  connect- 


TONGUE 


233 


ive  tissue.  Some  of  these  striated  fibers  are  branched.  The  muscula- 
ture of  the  tongue  is  partly  divided  into  right  and  left  halves  by  a 
dense  median  connective  tissue  partition,  the  septum  lingua,  which  begins 
low  on  the  hyoid  bone,  attains  its  greatest  height  in  the  middle  of  the 
tongue,  and  becomes  lower  anteriorly  until  it  disappears.  It  does  not 
extend  clear  through  the  tongue  since  it  ends  3  mm.  beneath  the  dorsum. 
The  muscles  of  the  tongue  are  partly  vertical  (Mm.  genioglossus ,  hyo- 
glossus,  and  verticalis  lingua},  partly  longitudinal  (Mm.  styloglossus, 
chondroglossus,  superior  and  inferior  longitudinalis  lingua}  and  partly 


Tuica  propria 


Secondary  papillae.     Taste  bud. 

Vallate  papilla. 
Groove*.    \ 
\ 


Orifice 

of  a  Small 

serous       papilla, 
gland. 


Epithelium. 


Tunica 
propria 


Striated 
muscle. 


\ 


Muscle  fibers  in  cross 
and  longitudinal  section. 


Nerve  with         Fascia  Mucous 

ganglion  cells,      linguae.  gland. 

FIG.  223. — VERTICAL  SECTION  OF  A  HUMAN  VALLATE  PAPILLA.     X  25. 


Vein. 


transverse  (M .  transversus  lingua).  The  glos  so  palatine  muscle  of  the 
palatine  group  also  enters  the  tongue.  Some  of  the  muscle  fibers  are  ob- 
lique but  many  of  the  bundles  cross  at  right  angles.  In  the  connective 
tissue  between  them,  medullated  nerves  are  abundant.  Some  are  sensory 
nerves  to  the  mucosa,  but  many  of  them  are  the  lingual  branches  of  the 
hypoglossal  nerve  which  supply  all  the  tongue  muscles  except  the  inferior 
longitudinal;  the  latter  is  supplied  by  fibers  from  the  chorda  tympani 
Sensory  spindles  have  been  found  in  the  lingual  muscles. 

Blood  vessels  are  numerous  in  the  submucosa  and  form  extensive 
capillary  networks  in  the  tunica  propria  of  both  primary  and  secondary 


234 


HISTOLOGY 


papillae.     Small  lymphatic  vessels  also  form  a  network  in  the   tunica 
propria,  and  this  is  continuous  with  a  coarser  net  in  the  submucosa. 

The  sensory  nerves  are  the  terminations  of  the  lingual  branches  of  the 
mandibular  nerve  anteriorly,  and  of  the  lingual  branches  of  the  glosso- 
pharyngeus  posteriorly.  In  the  submucous  connective  tissue  they  form 
a  plexus  of  medullated  and  non-medullated  fibers,  and  in  some  places, 
notably  beneath  the  valla te  papillae,  nerve  cells  are  found,  grouped  in 
small  ganglia  (Fig.  223).  The  terminal  branches  of  these  nerves  probably 
end  in  part  in  bulbous  corpuscles,  but  most  of  them,  as  non-medullated 


Taste  bud. 


Fibers  between 
the  buds 


Fibers  overlying 
a  bud. 


Connective  tissue. 
Epithelium. 


Fibers  within  the  buds. 


Connective  tissue. 


Nerve. 


FIG.  224. — FROM  A  VERTICAL  SECTION  OF  THE  FOLIATE  PAPILLA  OF  A  RABBIT.     X  220. 


fibers,  enter  the  epithelium  and  extend  to  the  outer  epithelial  cells,  gener- 
ally without  branching  (as  on  the  left  of  Fig.  2  24) .  Others  enter  the  groups 
of  specialized  epithelial  cells,  known  as  taste  buds,  which  are  believed  to 
be  the  special  organs  of  taste.  Within  the  buds  the  nerves  divide  into 
coarse  varicose  branches  which  end  freely,  without  uniting  with  the  cells 
or  anastomosing  with  one  another  (Fig.  224). 

Taste  buds  are  round  or  oval  groups  of  elongated  epithelial  cells,  most 
of  which  extend  from  the  basal  to  the  free  surface  of  the  epithelium.  In 
embryos  of  from  five  to  seven  months  they  are  more  numerous  than  in  the 
adult,  occurring  in  many  filiform  papillae,  in  all  the  fungiform,  vallate  and 
foliate  papillae,  and  also  upon  both  sides  of  the  epiglottis.  Subsequently 
they  are  destroyed  with  an  infiltration  of  leucocytes  except  on  the  lateral 
walls  of  the  vallate  and  foliate  papillae,  on  the  laryngeal  surface  of  the 


TONGUE 


235 


epiglottis,  and  a  small  portion  of  those  on  the  anterior  and  lateral  fungi- 
form  papillae.  These  remain  in  the  adult.  In  the  outer  half  of  each  bud 
the  cells  converge  like  the  segments  of  a  melon,  so  that  their  ends  are 
brought  together  in  a  small  area.  This  area  is  at  the  bottom  of  a  little  pore 
or  short  canal  found  among  the  outermost  flat  cells  of  the  epithelium. 
The  taste  pore  opens  treely  to  the  surface,  but  in  oblique  sections  it  may 
appear  bridged  as  in  Fig.  225. 
Within  the  bud  two  sorts 
of  elongated  cells  may  be  dis- 
tinguished, namely,  supporting 
cells  which  are  chiefly  peripheral, 
and  taste  cells  which  are  central. 
There  are  also  certain  cells  which 
lie  wholly  in  the  basal  part  of 
the  bud,  and  lymphocytes  which 
have  entered  the  bud  from  be- 
low are  frequently  seen  among 
the  other  cells.  The  support- 
ing '  cells  are  paler  than  the 
gustatory  cells,  and  may  be  uni- 
form in  diameter  or  tapering 
toward  their  ends;  they  are 
sometimes  forked  or  branched  below.  The  taste  cells  are  darker  and  more 
slender,  being  thickened  to  accommodate  the  narrow  nucleus  which  is 
usually  near  the  middle  of  the  cell.  At  the  taste  pore  these  cells  end  in 
a  stiff  refractive  process  which  is  a  cuticular  formation.  The  processes 
extend  into  the  deeper  part  of  the  pore  but  do  not  reach  its  outlet. 
These  cells  are  believed  to  transmit  the  gustatory  stimuli  to  the  nerves 
which  branch  about  them.  To  a  less  extent  the  nerves  are  said  to  ramify 
around  the  supporting  cells,  which  perhaps  have  other  functions  than 
their  name  implies. 


Taste  pore.    — " 


Supporting  ^** 
cells. 


Taste  cells.  "" 


Stratified 
epithelium. 


FIG.  225. — FROM  A  VERTICAL  SECTION  OF  A  HUMANA 
FOLIATE  PAPILLA.     X  330' 


Tunica 
propria. 


MOUTH  AND  PHARYNX. 

The  lining  of  the  mouth,  like  the  covering  of  the  tongue,  consists  of 
epithelium,  tunica  propria,  and  submucosa.  At  the  lips,  toward  the  line 
of  transition  from  skin  to  mucous  membrane,  hairs  disappear  from  the 
skin.  The  epithelium  becomes  thicker  but  more  transparent  as  it  crosses 
the  line  (Fig.  226).  Its  outer  cells  are  still  cornified,  but  they  are  not  so 
flat  and  compactly  placed  as  in  the  skin.  The  deeper  cells  appear  vesicular. 
Within  the  mouth,  except  on  the  tongue,  cornified  cells  are  absent,  but 
granules  of  the  refractive  horny  substance,  keratohyalin,  are  said  to  occur  in 
the  outer  cells,  even  in  the  oesophagus.  The  free  surface  of  the  epithelium 


236 


HISTOLOGY 


is  generally  smooth,  but  its  under  surface  is  indented  by  many  connective 
tissue  papillae,  which  are  particularly  long  and  slender  in  the  gums  and 
lips  (Fig.  226).  At  the  inner  border  of  the  lips  at  birth,  there  are  free 
papillary  projections  described  as  "true  villi,"  but  these  later  disappear. 
Cilia  are  found  on  the  oral,  pharyngeal  and  cesophageal  epithelia  in  the 
embryo,  but  in  the  adult  cilia  persist  only  in  certain  parts  of  the  pharynx. 

The  tunica  propria  in  the  mouth,  as  is  generally  the  case  in  the  digestive 
tract,  has  few  elastic  fibers.  Some  of  its  tissue  is  reticular,  and  in  it, 
lymphoid  accumulations  are  frequent;  they  may  extend  into  the  sub- 
mucosa.  On  the  oral  surface  of  the  soft  palate  there  is  a  layer  of  elastic 


Sebaceous  gland 
Tall  papillae 


Oblique  sec- 
tions of  papillae. 


Hair  shafts 
and  sebaceous 
glands. 


Sebaceous 
gland. 


Hair  shaft. 

Vein. 

Artery. 
"'  Bulb  of  a  hair. 


Submucosa.     Orbicular     Mimetic 
muscle.         muscle. 


Corium.     Epidermis. 


Epithelium.     Tunica 
propria. 

FIG.  226. — VERTICAL  SECTION  THROUGH  THE  LOWER  LIP  OF  A  MAN  OF  NINETEEN  YEARS.     X  10. 
Epidermis   and   corium    constitute  the  skin;  epithelium,  t.  propria,  and  submucosa  form  the    oral 

mucous  membrane. 


tissue  between  the  propria  and  submucosa.  A  similar  layer  is  found  in  the 
cesophageal  end  of  the  pharynx.  It  increases  in  thickness  upward,  at  the 
expense  of  the  submucosa,  so  that  it  forms  a  thick  layer  in  the  back  of  the 
pharynx  in  contact  with  the  muscles,  among  the  fibers  of  which  it  sends 
prolongations.  This  elastic  layer,  as  the  fascia  pharyngobasilaris,  is  at- 
tached to  the  base  of  the  skull. 

In  most  of  the  oral  region  there  is  no  sharp  line  of  separation  between 
the  propria  and  the  submucosa.  The  latter  may  be  a  loose  layer  contain- 
ing fat,  and  allowing  considerable  movement  of  the  mucosa,  or,  as  in  the 
gums  and  hard  palate,  it  may  be  a  dense  layer  binding  the  membrane 
closely  to  the  periosteum.  In  the  submucosa  are  the  branches  of  various 
glands.  On  the  inner  border  of  the  lips  and  the  inner  surface  of  the  cheek, 


MOUTH 

there  are  sebaceous  glands  without  hairs,  which  first  develop  during  puberty. 
This  type  is  described  with  the  skin.  The  other  oral  glands  are  considered 
in  the  following  section. 

GLANDS  OF  THE  ORAL  CAVITY. 

In  the  general  account  of  glands  (page  54)  it  has  been  stated  that 
serous  gland  cells  which  produce  a  watery  albuminoid  secretion  should  be 
distinguished  from  the  mucous  gland  cells  which  elaborate  thick  mucus. 
When  examined  fresh,  serous  cells  are  seen  to  contain  many  highly  refract- 
ive granules.  In  fixed  preparations  they  may  appear  dark  and  granular 
(empty  of  secretion)  or  enlarged  and  somewhat  clearer  (full  of  secretion), 
as  shown  in  Fig.  44,  p.  54.  The  round  nucleus  is  generally  in  the  basal 
half  of  the  cell,  not  far  from  its  center  (Fig.  227).  Mucous  cells  when 

Man.  Rabbit.  Man. 


Mucous  glands.  Serous  glands. 

TUBULES,  FROM  LINGUAL  GLANDS,  ILLUSTRATING  THE  DIFFI 

Mucous  AND  SEROUS  GLAND  CELLS. 
b,  Empty  mucous  cells;  c,  mucous  cells  full  of  secretion;  d,  lumen  of  the  tubule.     X  240. 


PIG.  227. — SECTIONS  OF  TUBULES,  FROM  LINGUAL  GLANDS,  ILLUSTRATING  THE  DIFFERENCES  BETWEEN 

Mucous  AND  SEROUS  GLAND  CELLS. 


fresh  are  much  less  refractive  than  serous  cells.  In  fixed  preparations 
they  are  typically  clear,  since  the  large  area  occupied  by  mucous  secretion 
stains  faintly.  Fully  elaborated  mucus,  however,  may  be  colored  intensely 
with  certain  aniline  dyes,  such  as  mucicarmine  and  Delafield's  haematoxy- 
lin.  In  certain  types  of  mucous  cells  the  pale  secretion  area  is  large  in 
all  stages  of  activity.  When  full  of  mucus,  the  nucleus  is  flattened  against 
the  base  of  the  cell,  and  when  empty,  the  nucleus  becomes  more  oval  with- 
out essentially  changing  its  position  (Fig.  227).  This  differs  from  the  type 
of  mucous  cell  found  in  the  gastric  epithelium,  in  which  the  secretion  area 
varies  considerably  with  the  elaboration  and  discharge  of  secretion  (Fig. 

45,  P-  55)- 

Glands  may  consist  entirely  of  serous  or  of  mucous  cells,  but  frequently 

they  include  cells  of  both  sorts  and  are  called  mixed  glands.  The  mixed 
glands  contain  some  purely  serous  tubules  or  alveoli;  the  rest  consist  of 
both  mucous  and  serous  cells,  so  arranged  that  the  latter  appear  more  or 
less  crowded  away  from  the  lumen.  Often  they  form  a  layer  outside  of 
the  mucous  cells,  partly  encircling  the  tubule  or  alveolus  and  constituting 
a  crescent  (demilune),  as  shown  in  Fig.  237.  The  serous  cells  of  the  cres- 


238 


HISTOLOGY 


~ 7 Axial  lumen. 


cent  are  connected  with  the  lumen  by  means  of  secretory  capillaries  (p.  57) 
which  pass  out  to  them  between  the  mucous  cells  and  branch  around  the 
serous  cells,  ending  blindly  (Fig.  228).  Sometimes  the  cells  of  the  crescent 
are  directly  in  contact  with  the  lumen.  Since  the  serous  crescents  are 
always  associated  intimately  and  somewhat  irregularly  with  mucous  cells, 

they  were  naturally  interpreted  as  a  func- 
tional phase  of  the  latter.  It  is  probably 
true  that  some  crescents  represent  empty 
mucous  cells  which  have  been  crowded 
from  the  lumen  by  those  full  of  secretion. 
No  secretory  capillaries  lead  to  such 
mucous  crescents,  which  moreover  are 
not  abundant.  Another  sort  of  crescen- 
tic  figure  is  made  by  the  basal  protoplasm 
FIG.  228.— FROM  A  SECTION  OF  THE  SUBMAX-  in  mucous  cells  otherwise  full  of  secre- 

ILLARY  GLAND  OF  A  DOG.     X  320. 

tion.  Finally,  in  oblique  sections,  stel- 
late cells  associated  with  the  basement  membrane  may  resemble  true 
crescents. 

The  oral  glands  include  serous  glands,  mucous  glands,  and  mixed  glands 
to  be  described  in  turn. 


Intercellular 
secretory 
capillary. 


Serous  Glands. 

The  serous  oral  glands  are  the  parotid  glands  and  the  serous  glands 
of  the  tongue  (v.  Ebner's  glands).  The  latter  are  branched  tubular 
glands  limited  to  the  vicinity  of  the  vallate  and 
foliate  papillae.  Generally  they  open  into  the 
grooves  which  bound  these  papillae.  Their  ducts 
are  lined  with  simple  or  with  stratified  epithelium, 
which  is  occasionally  ciliated.  Their  small  tub  tiles 
consist  of  a  delicate  membrana  propria  or  basement 
membrane,  which  surrounds  the  low  columnar  or 
conical  serous  cells.  In  this  simple  epithelium, 
cell  walls  are  lacking.  With  special  stains  and 
high  magnification,  a  dark  granular  zone  toward 
the  lumen  has  been  distinguished  from  the  clear 
basal  portion  of  the  cell  which  contains  the  nu- 
cleus (Fig.  229).  The  lumen  of  the  tubules  is 
very  narrow  and  receives  the  still  narrower  intercellular  secretory  capil- 
laries (Fig.  230). 

The  parotid  glands  are  the  largest  oral  glands.  Each  is  situated  in 
front  of  the  ear  and  is  folded  around  the  ramus  of  the  mandible;  its  duct, 
the  parotid  duct  (Stenson's),  empties  into  the  mouth  opposite  the  second 


FIG.  229. — TUBULE  OF  A  SER- 
OUS GLAND  FROM  THE  HU- 
MAN TONGUE.  X  750. 

Secretory  granules  toward  the 
lumen  are  finer  than-,  those 
further  out.  The  light  in- 
tercellular lines  represent  the 
secretory  capillaries. 


PAROTID   GLAND 


239 


molar  tooth  of  the  upper  jaw.  The  parotid  gland  is  an  organic,  branched 
serous  gland,  subdivided  into  lobes  and  lobules.  The  accessory  parotid 
gland  appears  as  a  lobe  separated  from  the  others.  The  parotid  duct  is 


Intercellular 
[secretory 
[capillaries.    ; 


FIG.  230. — SECTION  OF  A  SEROUS  GLAND 
FROM  THE  TONGUE  OF  A  MOUSE.  X  240. 

Prepared  by  Golgi's  method,  a  precipitate 
has  formed  in  the  ducts.  The  right 
lower  part  of  the  figure  has  been  com- 
pleted by  adding  the  cell  outlines. 


Membrane.       W^^Wl 


Lumen 

Terminal  bars. 


FIG.  231. — PART  OF  A  CROSS  SECTION  OF 
THE  SECRETORY  DUCT  FROM  LTHE 
PAROTID  GLAND  OF  A  MOUSE. 

The  basal  rods  (mitochondria)  toward  the 
lumen  break  apart  into  secretory 
granules. 


Secretory 
duct. 


Intercalated 
duct. 


End  piecees. 


PIG.  232. — DIAGRAM  OF  THE  HU- 
MAN PAROTID  GLAND. 


Fat  cells. 


End  piece.   -      ' 


Intercalated/''' 
duct. 


FIG.  233. — SECTION  OF  THE  PAROTID  GLAND  OF  AN  ADULT 

X  252. 
The  very  narrow  lumen  of  the  alveolo-tubular  end  pieces 

shown. 


MAN. 
is  not 


characterized  by  a  thick  membrana  propria,  and  consists  of  a  two-layered 
columnar  epithelium  with  occasional  goblet  cells.  As  the  duct  branches 
repeatedly,  the  epithelium  becomes  a  simple  columnar  epithelium,  after 


240 


HISTOLOGY 


being  pseudostratified,  with  two  rows  of  nuclei  (cf.  Fig.  39,  p.  49).  Pos- 
sibly the  epithelium  near  the  outlet  of  the  duct  is  also  pseudostratified. 
This  excretory  portion  of  the  duct  is  followed  by  the  secretory  part,  formed 
of  simple  columnar  cells  with  basal  striations,  perhaps  indicative  of  secre- 
tory activity  (Fig.  231).  As  shown  in  the  diagram  (Fig.  232)  and  in  the 
section  (Fig.  233)  the  secretory  ducts  become  slender,  forming  the  inter- 
calated ducts.  These  are  lined  with  flat  spindle-shaped  cells  which  are 
continuous  with  the  large  cuboidal  serous  cells  of  the  terminal  alveoli. 
The  gland  cells  when  empty  of  secretion  are  small  and  darkly  granular, 


Secretory 
ducts. 


b, Fat  cells. 


Blood  vessel. 


\  Intercalated 
/     ducts. 


Interlobular 
septum. 


— Alveoli. 


FIG.  234. — SECTION  OF  THE  PAROTID  GLAND  FROM  A  MAN  OF  TWENTY-THREE  YEARS.    X  100. 

Portions  of  three  lobules  are  shown,  which  have  drawn  apart  from  one  another  in  the  process  of  preparation. 

Note  the  abundance  of  secretory  ducts. 

and  when  full  are  larger  and  clearer.  They  rest  upon  a  basement  mem- 
brane containing  stellate  cells.  Intercellular  secretory  capillaries  end 
blindly  before  reaching  the  basement  membrane. 

Between  the  alveoli,  which  are  somewhat  elongated  and  branched, 
there  is  vascular  connective  tissue  containing  fat  cells.  In  denser  form 
it  surrounds  the  lobules  and  lobes  of  the  gland,  and  the  larger  ducts.  The 
ducts  which  are  found  in  the  connective  tissue  septa  are  called  interlobular 
ducts,  in  distinction  from  those  which  are  surrounded  by  the  alveoli  in 
which  they  and  their  branches  terminate.  The  latter  are  intralobular 
ducts.  They  are  smaller  and  have  less  connective  tissue  around  them  than 
the  interlobular  ducts,  of  which,  however,  they  are  continuations. 


PAROTID    GLAND  241 

Vessels  and  Nerves.  The  arteries  generally  follow  the  ducts  from  the 
connective  tissue  septa  into  the  lobules,  where  they  produce  abundant 
capillary  networks  close  to  the  basement  membranes.  The  veins  derived 
from  'these  soon  enter  the  interlobular  tissue,  and  may  then  accompany 
the  arteries.  The  lymphatic  vessels  follow  the  ducts,  and  branch  in  the 
interlobular  connective  tissue,  in  which  they  terminate.  Only  tissue  spaces 
have  been  found  within  the  lobules.  The  nerve  supply  is  from  several 
sources.  Sympathetic  nerves  from  the  plexus  around  the  carotid  artery 
accompany  the  blood  vessels  into  the  parotid  gland,  and  by  controlling 
the  blood  supply  have  an  important  bearing  upon  secretion.  The  nerves 
which  reach  the  gland  cells  are  in  connection  with  the  tympanic  branch 
of  the  glossopharyngeal  nerve.  This  branch  extends  to  the  otic  ganglion, 
from  which  fibers  pass  to  the  parotid  gland  by  way  of  an  anastomosis 
with  the  auriculo-temporal  branch  of  the  mandibular  nerve.  Within  the 
gland  the  nerves  pass  along  the  ducts,  where  they  are  associated  with 
microscopic  ganglia,  and  form  plexuses  beneath  the  basement  membranes 
of  the  alveoli.  From  these  plexuses,  fibers  penetrate  the  basement  mem- 
branes and  form  simple  or  branched  varicose  endings  in  contact  with  the 
gland  cells.  Other  nerves  enter  the  substance  of  the  gland,  either  to  pass 
through  it  or  to  contribute  to  its  nerve  supply;  these  include  branches 
of  the  trigeminal,  facial  and  great  auricular  nerves,  the  last  coming  from 
the  second  and  third  cervical  nerves.  Free  sensory  endings  of  medullated 
fibers  are  said  to  occur  in  the  epithelium  of  the  ducts 

Mucous  Glands. 

The  purely  mucous  glands  of  the  mouth  are  simple  branched  alveolo- 
tubular  glands  found  on  the  anterior  surface  of  the  soft  palate  and  on  the 
hard  palate  (palatine  glands),  along  the  borders  of  the  tongue  (lingual 
glands),  and  in  greater  numbers  in  the  root  of  the  tongue.  There  they 
may  open  into  the  tonsillar  pits  through  ducts  lined  with  columnar  epi- 
thelium, sometimes  ciliated.  The  wall  of  the  tubules  consists  of  a  struc- 
tureless basement  membrane  and  of  columnar  mucous  cells,  varying  ac- 
cording to  their  functional  condition  as  shown  in  Fig.  227,  I-II.  The 
empty  cells  are  narrower  than  the  others,  and  the  nuclei,  though  at 
the  base  of  the  cell  and  transversely  oval,  are  not  as  flat  as  in  cells 
full  of  secretion.  Seldom  can  cells  be  found  completely  occupied  by 
unaltered  protoplasm.  A  single  gland,  or  even  a  single  alveolus,  may 
contain  cells  in  different  phases  of  secretion,  as  is  clearly  seen  when  special 
mucin  stains  are  used.  Secretory  capillaries  are  not  found  in  the  purely 
mucous  glands. 

Mixed  Glands. 

The  mixed  oral  glands  are  the  sublingual,  submaxillary,  anterior  lin- 
gual, labial,  buccal,  and  molar  glands.  They  all  possess  crescents  of 

16 


242  HISTOLOGY 

serous  cells  such  as  are  to  be  described  in  the  largest  glands  of  this  group — 
the  sublingual  and  submaxillary. 

The  sublingual  glands  are  two  groups  of  glands,  one  on  either  side  of 
the  median  line,  under  the  mucous  membrane  in  the  front  of  the  mouth. 
The  largest  component  is  an  alveolo- tubular  structure  emptying  by  the 
•i  ductus  sublingualis  major  on  the  side  of   the 

frenulum  lingua.  The  main  stem  and  the 
principal  branches  of  the  large  sublingual  duct 
are  lined  by  a  two-layered  or  pseudostratified 
columnar  epithelium,  as  in  the  parotid  duct. 
They  are  surrounded  by  connective  tissue  con- 
taining many  elastic  fibers.  Ducts  less  than 
.05  mm.  in  diameter  have  a  simple  columnar 
epithelium,  which  in  a  few  places  becomes  low 
and  basally  striated  to  form  the  secretory 
ducts.  As  shown  in  the  diagram,  Fig.  235,  the 
secretory  ducts  are  very  short,  and  they  are 
:es-  accordingly  infrequent  in  sections;  the  slender 
intercalated  ducts  are  absent.  The  terminal 
FIG.  235—DiAGRAM  OF  THE  HUMAN  secreting  portions  of  the  gland  are  somewhat 

tortuous  structures,  often  presenting  outpock- 

etings.  They  consist  of  mucous  and  serous  cells  quite  evenly  mixed,  so 
.  that  the  gland  has  a  characteristic  appearance  under  low  magnification 
(Fig.  236).  The  serous  cells  sometimes  border  upon  the  lumen,  but  often 
they  are  separated  from  it  by  the  mucous  cells  so  that  they  form  crescents 
(Fig.  237).  Only  the  serous  cells  are  provided  with  the  branched  inter- 
cellular secretory  capillaries.  Around  the  tubules  there  is  a  basement 
membrane  including  certain  stellate  cells.  The  interlobular  connective 
tissue  contains  many  lymphocytes. 

Near  the  gland  just  described,  but  apparently  quite  distinct  from  it, 
there  is  a  group  of  5  to  20  alveolo-tubular  glands  which  open  by  separate 
ducts,  the  ductus  sublinguales  minores.  These  glands  consist  almost  ex- 
clusively of  mucous  cells. 

The  sublingual  gland  as  a  whole  receives  fibers  from  the  submaxillary 
ganglion,  and  so  from  the  chorda  tympani,  which  passes  to  this  ganglion 
by  way  of  an  anastomosis  with  the  lingual  branch  of  the  mandibular  nerve. 
Its  ducts  are  said  to  have  sensory  fibers,  probably  derived  from  the  lingual 
nerve.  Sympathetic  fibers  from  the  superior  cervical  ganglion,  which 
have  ascended  the  neck  as  perivascular  plexuses,  extend  to  the  sublingual 
gland  around  its  arteries. 

The  submaxillary  glands  are  a  pair  of  branched  alveolar  glands,  in  part 
tubulo- alveolar,  found  in  the  floor  of  the  mouth,  each  being  drained  by  a 
submaxillary  duct  (Wharton's)  which  opens  on  the  sides  of  the  frenulum 


SUBLINGUAL   GLAND 


243 


Secretory  duct. 


Crescent  of  six 
serous  cells. 


Lymphoid  tissue. 
Secretory  duct. 

—  Connective  tissue. 

__.  Serous  cells. 
Mucous  cells. 


FIG.  236. — SECTION  OF  THE  SUBLINGUAL  GLAND  (GL.  SUBL.  MAJOR)  FROM  A  MAN  OF  TWENTY-THREE 

YEARS.     X  100. 


A  crescent  consisting  of 
eight  serous  cells. 


Part  of  an  excretory  duct. 


Lumen 


Tangential 

section  of  serous 

cells. 


Mucous  cells  and 

thick  membrana 

propria. 


m 

FIG.  237. — SECTION  OF  A  HUMAN  SUBLINGUAL  GLAND.     X  252. 


244 


HISTOLOGY 


Excretory 
duct. 


lingua?  near  its  front  margin.  Sometimes  this  duct  is  joined  by  the  ductus 
sublingualis  major  so  that  the  two  have  a  common  outlet.  Its  orifice  may 
be  lined  by  stratified  epithelium,  but  this  soon  gives  place  to  the  two  layered 
form.  Secretory  ducts  are  well  developed  (Fig.  238)  and  their  basally 

striated  cells  contain  a  yellow  pigment.  The 
intercalated  ducts,  which  are  lined  with  sim- 
ple cuboidal  epithelium,  lead  to  terminations 
of  two  sorts.  Most  of  these  consist  entirely 
of  serous  cells.  The  others  are  mixed,  but 
the  crescents  are  small,  composed  of  only  a 
few  or  even  of  single  serous  cells  (Figs.  239 
and  240).  Secretory  capillaries  such  as  have 
already  been  described,  are  related  only  to 
t^ie  serous  ce^s-  Elastic  tissue  surrounding 
intercalated  the  alveoli  has  been  thought  to  aid  in  ex- 
pelling  the  secretion  through  the  ducts.  The 
nerves  have  the  same  origin  as  those  of  the 
sublingual  gland. 

In  the  oral  glands,  not  infrequently  de- 


Secretory 
duct. 


End  pieces. 


FIG.   238. — DIAGRAM   OF   THE  HUMAN 
SUBMAXILLARY  GLAND. 


generating  lobules  occur,  characterized  by 
abundant  connective  tissue  between  tubules  with  wide  lumens  and  low 
gland  cells.  Sometimes  they  are  surrounded  by  leucocytes. 


Serous  gland  cells. 
Pv-Jt?         \  *m\    Intercalated  duct. 

*?>  75W\ 


Mucous 
gland  cells. 


Connective  tissue. 


Lumen. 


'*  1;F* 

V^tef" 

Crescent.  Secretory  duct. 

FIG.  239. — SECTION  OF  THE  SUBMAXILLARY  GLAND  OF  AN  ADULT  MAN.     X  252. 


SUBMAXILLARY   GLAND 


245 


Serous    Intercalated    Blood, 
cells.  duct.  vessels 


Secretory 
duct. 


Mucous  cells. 


Connective  tissue. 


Fat  cells. 


II 


FIG.  240.— SECTION  OF  THE  SUBMAXILLARY  GLAND  FROM  A  MAN  OF  TWENTY-THREE  YEARS.     X   100. 

Note  that  the  serous  cells  predominate,  and  that  secretory  ducts  are  abundant.     (A  characteristic 

crescent  is  shown  at  x.) 


THE  DEVELOPMENT  OF  THE  DIGESTIVE  TUBE. 

The  digestive  tube  of  mammals  arises  as  two  outgrowths  from  the 
yolk-sac — the  fore-gut  and  hind-gut  respectively.  They  are  shown  in 
Fig.  241,  A,  w-hich  represents  a  young  rabbit  embryo  placed  in  a  vertical 
position.  Most  of  the  spherical  yolk-sac  has  been  cut  away.  Anteriorly 
the  fore-gut  (ph)  is  seen  extending  from  the  yolk-sac  to  the  oral  plate; 
posteriorly  the  sac  has  given  rise  to  a  short  hind -gut  from  which  a  tubular 
ventral  outgrowth,  the  allantois,  has  begun  to  develop.  The  allantois 
will  be  described  with  the  membranes  which  surround  the  embryo.  In 
an  older  stage  (Fig.  241,  B)  the  fore-gut  and  hind-gut  have  elongated, 
and  the  connection  of  the  tube,  which  they  form,  with  the  yolk-sac  is 
becoming  reduced  to  a  slender  stalk.  The  entodermal  tube  within  the 
stalk  is  called  the  mtelline  duct.  .  Posteriorly  the  intestine  and  allantois 
unite  and  form  the  cloaca,  which  is  closed  to  the  exterior  by  the  cloacal 
membrane.  (The  marked  bend  in  the  intestinal  tube  shown  in  Fig.  241,  B, 
which  is  often  seen  in  human  embryos,  is  exaggerated,  if  not  produced 
altogether,  by  a  post-mortem  sagging  of  the  yolk-sac.) 


246 


HISTOLOGY 


In  the  later  stage  (Fig.  241,  C)  both  the  fore-gut  and  hind-gut  have 
greatly  elongated;  together  they  form  a  loop  of  intestine  extending  out 
into  the  cavity  of  the  umbilical  cord.  Near  the  bend  in  this  loop  the 
yolk-sac  is  still  attached  to  the  intestine  by  a  stalk;  the  sac  itself  has  been 
cut  away  in  the  figure.  In  addition  to  the  pharynx  already  described,  the 


al 


FIG.  241. — STAGES  IN  THE  DEVELOPMENT  OF  THE  DIGESTIVE  TUBE.     A.  Rabbit  of  nine  days.     B.  Man 

2.15  mm.  (after  His).     C.  Pig,  12  mm.     D.  Man,  17.8  mm.  (after  Thyng).     E.  Man,  about  five  months. 
a.,  Anus;  al.,  allantois;  bl.,  bladder;  cae.,  bulb  of  the  colon;  cl.,  cloaca;  du.,  duodenum;  1.  L,  large  intestine; 

oe.,  oesophagus;  p.,  penis;  pe.,  perineum;  ph.,  fore-gut;  r.,  rectum;  s.  i.,  small  intestine;  St.,  stomach; 

u.  c.,  umbilical  cord;  ur.,  urethra;  ura.,  urachus;  u.  s.,  urogenital  sinus;  v.  p.,  vermiform  process; 

y.  s.,  yolk-sac;  y.  St.,  vitelline  duct  within  the  yolk-stalk. 


fore-gut  has  given  rise  to  an  expanded  portion  or  stomach.  Between  the 
stomach  and  pharynx  it  remains  tubular  and  becomes  the  oesophagus; 
posterior  to  the  stomach  it  is  likewise  tubular  and  there  it  forms  a  part 
of  the  small  intestine.  The  first  portion  of  the  small  intestine  is  called  the 
duodenum,  and  is  followed  by  the  jejunum  which  passes  without  demarca- 
tion into  the  ileum.  The  ileum  includes  the  portion  to  which  the  yolk- 
stalk  is  attached,  and  terminates  at  a  bulbous  enlargement  (Fig.  241,  C, 
cae)  which  gives  rise  to  the  ccecum  and  vermiform  process.  This  bulbus 
coli  (Johnson)  marks  the  beginning  of  the  large  intestine  or  colon,  and 
the  caecum  and  vermiform  process  are  parts  of  the  large  intestine.  Toward 
the  cloaca  the  colon  becomes  the  rectum,  and  near  its  termination  it  forms 
an  elongated  bulbous  enlargement,  the  bulbus  analis.  As  shown  by  F.  P. 


THE    DIGESTIVE   TUBE  247 

Johnson  (in  a  paper  about  to  be  published)  this  bulb  forms  essentially 
the  zona  columnaris  in  the  anal  part  of  the  rectum.  The  anus  is  produced 
after  the  cloaca  has  separated  into  dorsal  and  ventral  portions.  The 
ventral  division,  which  carries  with  it  the  allantois,  becomes  expanded  to 
form  the  bladder,  but  its  outlet  remains  relatively  narrow  and  becomes  the 
urethra.  The  outlet  of  the  rectum  is  the  anus,  which  is  at  first  closed  by 
the  anal  membrane;  this  membrane  ruptures  in  embryos  measuring  from 
20  to  30  mm.,  except  in  the  occasional  cases  of  imperforate  anus.  The 
tissue  which  subdivides  the  cloaca  reaches  the  surface  and  constitutes  the 
perineum. 

In  human  embryos  of  about  10  mm.  the  intestinal  loop  becomes  twisted 
on  itself  (Fig.  241,  D),  and  the  large  intestine  is  carried  across  the  small 
intestine  in  the  duodenal  region.  The  vermiform  process  thus  comes  to 
lie'on  the  right  side  of  the  body,  and  the  colon,  after  it  is  withdrawn  from 
the  umbilical  cord  into  the  body,  is  so  bent  as  to  form  ascending,  transverse, 
and  descending  portions,  below  which,  as  the  convoluted  sigmoid  colon, 
it  connects  with  the  rectum.  The  disposition  of  the  adult  intestines  de- 
pends chiefly  upon  this  primary  torsion  of  the  intestinal  loop,  and  upon 
the  subsequent  elongation  of  the  small  intestine,  which  forms  many  loops 
and  coils. 

Meanwhile  the  yolk-sac  has  become  detached,  and  its  stalk  has  dis- 
appeared, usually  leaving  no  indication  of  its  former  position.  The  stalk 
does  not  become  the  vermiform  process,  as  was  once  supposed,  but  occa- 
sionally it  produces  a  blind  pouch  of  the  ileum,  3-9  cm.  long,  situated  about 
three  feet  above  the  beginning  of  the  colon.  This  is  the  diverticulum  ilei, 
described  and  correctly  interpreted  by  Meckel  in  1812. 

The  division  of  the  intestine  into  six  parts  is  a  heritage  from  the  Arabians.  Duo- 
denum, jejunum,  ileum,  caecum,  colon  and  rectum  were  well  recognized  in  the  fifteenth 
century,  when,  following  Hippocrates,  they  were  counted  from  below  upward.  The 
various  names  which  have  been  applied  to  them  are  discussed  by  Hyrtl  (Das  arabische 
und  hebraische  in  der  Anatomic,  Wien,  1879).  Those  which  are  now  adopted  have  the 
following  significance.  The  rectum  is  the  straight  terminal  portion.  "Colon  is  the 
xwAov  of  Aristotle,  which  according  to  Pliny  is  a  great  source  of  pain  (colic)."  The 
caecum,  or  blind  intestine,  was  so  named  by  Galen,  who  did  not  practice  human  dis- 
section and  so  referred  to  the  more  elongated  pouch  in  lower  animals.  The  name  has 
generally  been  considered  inappropriate  for  the  human  caecum.  The  Greek  synonym 
rv<f>Xbv  (blind)  is  used  in  the  medical  term  typhlitis  (inflammation  of  the  caecum). 
The  ileum  (from  etAe'w)  is  the  coiled  portion,  and  is  arbitrarily  defined  as  the  lower 
three-fifths  of  the  small  intestine.  The  jejunum  (Lat.,  fasting)  is  the  portion  generally 
found  void  and  empty  (Avicenna),  since  food  passes  through  it  rapidly.  The  duode- 
num, which  has  no  free  mesentery,  was  originally  considered  a  part  of  the  stomach; 
its  name  indicates  that  its  length  is  twelve  finger-breadths.  Hyrtl  notes  that  the  same 
term  has  sometimes  been  applied  to  the  rectum. 

Layers  of  the  Digestive  Tube.    The  wall  of  the  digestive  tube  is  com- 


248  HISTOLOGY 

posed  of  four  layers — (i)  tunica  mucosa,  (2)  tela  submucosa,  (3)  tunica 
muscularis,  and  (4)  tunica  adventitia  or  tunica  serosa.  The  parts  which 
are  covered  with  peritoneum  have  a  serous  coat  for  their  outer  layer;  the 
parts  imbedded  in  connective  tissue  have  the  adventitious  coat  instead. 

The  tunica  mucosa  consists  of  epithelium,  tunica  propria,  and  the 
lamina  muscularis  mucosa.  The  epithelium  is  the  en  to  dermal  lining  of 
the  tube,  and  is  folded  and  inpocketed  so  as  to  form  innumerable  pits  and 
glands,  varying  in  their  nature  in  different  parts  of  the  tube.  The  tunica 
propria  consists  of  reticular  tissue,  which  in  places  becomes  characteristic 
lymphoid  tissue.  It  is  set  apart  early  in  development  as  a  layer  with 
abundant  nuclei,  thus  differing  from  the  underlying  mesenchyma.  At  a 
later  stage  the  lamina  muscularis  mucosa,  or  muscle  layer  of  the  mucous 
membrane,  develops  beneath  it,  separating  it  from  the  submucosa.  The 
muscularis  mucosae  is  a  thin  layer  of  smooth  muscle  fibers. 

The  tela  submucosa  (tela,  tissue)  is  a  connective  tissue  layer  which 
contains  many  blood  and  lymphatic  vessels,  and  the  ganglionated  plexus 
submucosus. 

The  tunica  muscularis  usually  consists  of  an  inner  circular  and  an  outer 
longitudinal  layer  of  smooth  muscle  fibers,  separated  by  a  thin  layer  of 
connective  tissue  which  contains  the  ganglionated  plexus  myentericus. 

The  tunica  serosa  is  a  connective  tissue  layer,  covered  by  the  peritoneal 
epithelium. 

The  layers  enumerated  are  to  be  examined  in  the  oesophagus,  stomach 
and  intestine,  which  differ  from  one  another  histologically,  since  these 
layers  are  variously  modified. 

(ESOPHAGUS. 

The  oesophagus  is  a  tube  about  nine  inches  long,  the  several  layers 
of  which  are  continuous  anteriorly  with  those  of  the  pharynx,  and  poste- 
riorly with  those  of  the  stomach.  The  mucous  membrane  is  thrown  into 
folds,  except  when  the  tube  is  distended  by  the  passage  of  food;  but  the 
muscularis  merely  thickens -on  contraction,  so  that  it  always  forms  a  smooth 
round  layer  (Fig.  242). 

The  epithelium  is  thick  and  stratified  like  that  of  the  pharynx.  Its 
outer  cells  are  flattened  in  the  adult,  but  in  the  embryo  they  include  nu- 
merous islands  of  tall  ciliated  cells,  some  of  which  are  found  at  birth.  The 
basal  surface  of  the  epithelium  rests  upon  connective  tissue  papillae  or 
ridges. 

The  glands  of  the  oesophagus  are  of  two  sorts,  superficial  and  deep. 
The  deep  glands  (glandulce  msophagecz  produnda)  develop  as  scattered 
tubular  downgrowths  which  pass  through  the  tunica  propria  and  muscu- 


OESOPHAGUS 


249 


laris  mucosae  into  the  submucosa,  where  their  blind  ends  expand  and 
branch,  producing  a  cluster  of  tubulo-alveolar  end  pieces.  The  terminal 
portions  at  birth  are  still  poorly  developed.  The  tubules  are  composed 
wholly  of  mucous  cells,  although  the  basal  protoplasm  sometimes  simulates 
crescents.  The  ducts  are  slender  tubes  generally  lined  with  simple  epi- 
thelium. They  tend  to  slant  toward  the  stomach,  and  they  enter  the 
epithelium  where  it  dips  down  between  the  connective  tissue  papillae.  The 
cells  of  the  ducts  become  continuous  with  the  basal  layer  of  the  epithelium. 
Large  ducts  are  sometimes  lined  with  stratified  epithelium,  often  ciliated, 
and  they  may  present  cyst-like  dilatations.  Lymphocytes  tend  to  accumu- 


Stratified  epithe- 
lium. 


Mucous 
membrane. 


Group  of       X, 
fat  cells. 


\ 

\Circular  muscles.   ) 
Longitudinal  mus-  VMuscularis. 
cles.  J 


'Mucous  gland. 


xTunica  adventitia. 


Lymph  nodule. 
FIG.  242. — TRANSVERSE  SECTION  OF  THE  UPPER  THIRD  OF  THE  HUMAN  (ESOPHAGUS.        X  5. 

late  around  the  ducts  and  occasionally  they  form  nodules  in  the  tunica 
propria.  The  glands  may  show  signs  of  infiltration  and  degeneration. 
The  number  of  deep  glands  varies  greatly  in  different  individuals.  They 
are  usually  more  numerous  in  the  upper  half  of  the  oesophagus. 

The  superficial  glands  (glandules  cesophagece  superficiales)  are  limited 
to  two  rather  narrow  zones  near  the  ends  of  the  oesophagus.  They  are 
always  found  at  the  entrance  of  the  stomach,  extending  from  i  to  4  mm. 
up  the  oesophagus;  and  generally  (in  70%  of  the  cases  examined  by  Schaffer) 
they  occur/  between  the  level  of  the  cricoid  cartilage  and  fifth  tracheal 
ring.  They  develop  in  the  embryo  much  earlier  than  the  deep  glands, 
and  appear  as  small  areas  of  tall  mucous  cells  which  pass  clear  through 
the  stratified  epithelium.  These  islands  of  simple  epithelium  become 
depressed  into  shallow  pockets  from  which  a  cluster  of  tubules  grows 


250 


HISTOLOGY 


out,  but  they  never  pass  through  the  muscularis  mucosae  into  the  submu- 
cosa.  In  the  adult  the  upper  group  may  be  seen  with  the  naked  eye  as  an 
" erosion"  of  the  mucous  membrane.  The  glands  produce  a  form  of 
mucus  which  stains  less  readily  with  the  mucus-stains  than  that  of  the 
deep  glands.  No  special  function  has  been  assigned  to  this  secretion. 
Glands  of  the  lower  group  are  shown  in  Fig.  243.  They  are  freely  branch- 
ing mucous  glands,  the  ducts  of  which  open  at  the  tops  of  connective  tissue 
papillae.  They  very  frequently  show  cystic  enlargements. , 


d  e  f  g 

FIG.  243. — LONGITUDINAL  SECTION  THROUGH  THE  JUNCTION  OF  THE  HUMAN  OESOPHAGUS 

AND  STOMACH.     X  60. 

a,  Duct  of  a  superficial  cesophageal  gland;  b,  cesophageal  epithelium;  c,  gastric  epithelium;   d,  tubule  of 
the  gland  a;  e,  lymphoid  nodule;  f,  lymphatic  vessel;  g,  lamina  muscularis  mucosae. 

The  tunica  propria  in  the  oesophagus  has  fewer  cells  in  its  meshes  than 
that  of  the  lower  parts  of  the  digestive  tube.  In  places  it  includes  solitary 
lymph  nodules.  The  muscularis  mucosae  is  very  wide  in  the  oesophagus. 
It  is  a  layer  of  longitudinal  smooth  muscle  fibers,  which  is  thrown  into  longi- 
tudinal folds  when  the  oesophagus  is  contracted.  It  begins  anteriorly  at 
the  level  of  the  cricoid  cartilage,  arising  as  scattered  bundles  inside  the 
elastic  layer  of  the  pharynx.  As  the  muscles  increase  to  form  a  distinct 
layer,  the  elastic  lamina  terminates.  The  submucosa  is  a  loose  connective 
tissue  layer,  containing  many  vessels  and  nerves,  groups  of  fat  cells,  and 
the  bodies  of  the  deep  mucous  glands.  The  muscularis  consists  of  an  inner 
circular  and  an  outer  longitudinal  layer,  as  elsewhere  in  the  digestive  tube, 
but  in  the  upper  part  of  the  oesophagus  the  layers  #re  composed  of  striated 


(ESOPHAGUS  251 

muscle  fibers.  These  fibers  are  not  a  downward  extension  of  the  striated 
pharyngeal  constrictors,  but  apparently  develop  from  exactly  such  mesen- 
chymal  cells  as  produce  smooth  muscle  further  down.  The  striated 
muscles  in  man  are  limited  to  the  upper  half  of  the  oesophagus ;  in  the  rabbit 
they  extend  its  whole  length. 

The  adventitia  is  loose  connective  tissue,  containing  many  vessels  and 
the  plexiform  branches  of  the  vagus  nerves.  From  these  nerves,  medul- 
lated  and  non-medullated  fibers  enter  the  oesophagus  and  form  a  ganglion- 
ated  myenteric  plexus  between  the  muscle  layers,  and  the  plexus  submu- 
cosus  in  the  submucosa.  Medullated  fibers  proceed  from  the  vagus 
trunks  to  the  motor  end  plates  of  the  striated  muscles,  which  are  thus 
stimulated  reflexly  from  the  central  nervous  system.  Other  fibers  pass 
from  the  myenteric  plexus  to  the  plexus  submucosus  and  thence  to  the 
epithelium,  in  which  free  nerve  endings  have  been  found.  Such  fibers, 
together  with  those  to  the  smooth  muscles,  provide  for  local  reflex  action, 
whereby  the  contents  of  the  oesophagus  causes  contraction  above,  and  re- 
laxation below,  the  place  of  stimulation.  This  takes  place  independently 
of  the  central  system,  and  is  the  form  of  innervation  characteristic  of  the 
intestine. 

STOMACH. 

Form  and  Subdivisions.  The  opening  through  which  the  oesophagus  connects  with 
the  stomach  is  the  cardia  (Gr.  Ka/aSta,  heart),  and  the  opening  from  the  stomach  to  the 
intestine  is  the  pylorus  (Gr.  TrvAoopos,  gate-keeper).  The  pylorus  received  its  appropri- 
ate name  from  Galen  (in  the  second  century) ,  who  recognized  that  through  its  sphincter 
muscle  it  controlled  the  exit  of  food.  The  significance  of  cardia  was  discussed  by 
Fabricius  (1618)  who  cites  Galen  as  stating  that  the  upper  orifice  of  the  stomach  is 
called  the  heart  because  the  symptoms  to  which  it  gives  rise  are  similar  to  those  which 
sometimes  affect  the  heart,  sometimes  even  the  brain;  but  for  Fabricius,  cardia,  as 
applied  to  this  orifice,  merely  indicates  a  chief  part  of  the  body.  The  stomach  as  a 
whole  is  termed  gaster,  from  the  Greek,  but  the  Latin  ventriculus  was  generally  used 
by  the  early  anatomists.  Although  flaccid  and  shapeless  when  seen  in  the  dissecting 
room,  the  stomach  has  a  very  characteristic  form.  Its  epithelium,  from  an  embryo 
of  44.3  mm.,  is  shown  in  Fig.  244,  and  an  adult  stomach  is  seen  in  Fig.  250.  It  is  a 
tube  which  is  greatly  distended  toward  the  left,  where  its  border  forms  the  greater 
curvature;  its  right  border  is  the  lesser  curvature.  As  a  whole  the  stomach  is  divided 
into  two  parts,  the  cardiac  portion  (pars  cardiacd)  and  pyloric  portion  (pars  pylorica). 
This  fundamental  subdivision  occurs  in  many  animals,  as  was  recognized  by  Sir 
Everard  Home  in  1814.  The  pyloric  part  is  relatively  long  in  the  embryo.  It  becomes 
subdivided  into  the  pyloric  vestibule  and  the  pyloric  antrum.  The  latter  is  its  smaller 
part  extending  to  the  pylorus;  between  the  two,  on  the  greater  curvature,  is  the  sulcus 
intermedius,  well  shown  in  Fig.  250.  (The  term  pyloric  antrum  has  been  variously 
employed,  since  in  its  original  description  by  Willis  (1674)  the  vestibule  is  not  recog- 
nized; Cowper  (1698)  applies  antrum  to  the  terminal  subdivision  as  above  denned.) 
The  cardiac  part  of  the  stomach  is  divided  into  a  main  portion,  or  body  of  the  stomach 
(corpus  gastri),  and  a  blind  pouch,  formerly  called  the  saccus  caecus,  but  now  less 


252  HISTOLOGY 

appropriately  known  as  the  fundus  gastri  (the  bottom  of  the  stomach).  Recently 
the  gastric  canal  (canalis  gastri)  has  been  recognized  along  the  lesser  curvature  of  the 
human  stomach.  It  is  a  channel,  highly  developed  in  ruminants,  which  conveys  liquids 
from  the  cardia  to  the  pars  pylorica,  when  the  stomach  is  filled  with  more  solid  contents. 
Ordinarily  open  toward  the  interior  like  a  groove,  it  may  become  closed  as  a  tube 
during  its  physiological  activity.  Beyond  the  cardia  there  is  a  conical  expansion  of 
the  oesophagus,  not  always  well  defined,  known  as  the  cardiac  antrum,  and  beyond 
the  pylorus  is  the  first  part  of  the  duodenum,  or  du'odenal  antrum.  (A  further  account 
of  the  development  of  these  subdivisiods  will  be  found  in  the  Amer.  Journ.  Anat., 
1912,  vol.  13,  pp.  477-5°3-) 

(Esophagus. . 

Fundus. 


Gastric  canal. 
Angular  incisure. 


Pyloric       Pyloric 
antrum.  vestibule. 


Duodenal         Pvloric       Pvloric      \  I    JP  jRf 

antrum. 


FIG.  244. — MODEL  OF  THE  GASTRIC  EPITHELIUM  IN  A  HUMAN  EMBRYO  OF  44.3  MM.     X  18  diam. 

The  inner  surface  of  the  stomach  presents  macroscopic  longitudinal 
folds,  which  become  coarse  and  prominent  as  the  organ  contracts.  They 
are  sinuous,  and  anastomose  in  an  irregular  network.  As  finer  markings, 
there  are  rounded  or  polygonal  areas,  2-4  mm.  in  diameter,  which  may 
appear  as  elevations  or  depressions.  They  have  been  ascribed  to  the  con- 
traction of  muscle  fibers  in  the  mucous  membrane,  to  varying  amounts  of 
lymphoid  tissue,  and  to  the  varying  height  of  the  glands.  Toward  the 
pylorus  there  are  small  leaf-like  elevations,  the  plica  villosce,  which  may 
connect  with  one  another  in  a  network.  The  epithelium  of  the  stomach  is 
thin  enough  to  transmit  the  color  of  the  underlying  tissue,  and  appears 
pinkish  gray;  whereas  the  color  of  the  oesophagus,  with  a  thicker  epithelium, 
is  white. 

The  gastric  epithelium,  like  that  of  the  entire  intestine,  is  a  single  layer 
of  columnar  cells.  In  the  stomach  the  cells  are  tall  and  contain  mucus,  but 
they  do  not  ordinarily  acquire  the  bulging  goblet  shape,  since  the  adjacent 
cells  likewise  contain  mucus.  This  simple  layer  of  mucous  cells  is  con- 
tinuous at  the  cardia  with  the  basal  layer  of  the  stratified  epithelium  of  the 


STOMACH  253 

oesophagus,  and  the  transition  is  abrupt.  The  outer  strata  of  the  cesopha- 
geal  epithelium  may  form  an  overhanging  wall  (Fig.  243),  or  the  number  of 
layers  may  have  become  reduced  so  that  such  a  wall  is  absent.  Sometimes 
an  island  of  stratified  epithelium  occurs  just  beyond  the  line  of  transition. 
The  gastric  epithelium  forms  three  types  of  glands,  known  as  cardiac, 
gastric,  and  pyloric  glands  respectively,  none  of  which  extend  into  the 
submucosa. 

The  cardiac  glands  are  like  the  superficial  glands  at  the  lower  end  of  the 
oesophagus,  of  which  they  may  be  regarded  as  a  continuation.  They  ex- 
tend only  from  5  to  40  mm.  into  the  stomach,  and  in  the  narrow  zone  which 
they  occupy,  they  present  a  gradual  transition  to  the  gastric  glands. 
Their  branches,  instead  of  continuing  divergent,  become  groups  of  per- 
pendicular tubes  descending  from  epithelial  pits;  and  deeply  staining 
eosinophilic  cells  and  the  granular  chief  cells  become  included  in  their 
epithelium. 

The  cells  characteristic  of  the  cardiac  glands  contain  a  mucus  which 
does  not  respond  readily  to  mucin  stains.  Like  the  superficial  glands  of 
the  oesophagus,  the  cardiac  glands  develop  early,  and  they  are  found  widely 
distributed  among  mammals. 

The  gastric  glands  (sometimes  inappropriately  called  fundus  glands) 
occur  over  the  entire  surface  of  the  stomach,  except  near  the  cardia  and  py- 
lorus. Each  gastric  gland  is  divided  into  an  outer  portion,  or  gastric  pit 
(foveola  gastrica) ,  and  a  group  of  slender  cylindrical  tubules  which  empty 
into  the  bottom  of  the  pit.  During  development,  as  the  lining  of  the  stom- 
ach expands  greatly,  the  number  of  pits  increases.  Toldt  estimated  that 
there  were  129,912  in  the  stomach  at  three  months;  268,770  at  birth*  and 
2,828,560  at  ten  years.  The  increase  is  accomplished  by  division  of  the 
pits  from  below  upward.  In  spite  of  the  fact  that  many  new  branches 
develop,  the  average  number  of  tubules  emptying  into  each  pit  becomes 
reduced  as  the  pits  become  subdivided;  and  the  average  of  seven  per  pit 
observed  at  birth  becomes  three  in  the  adult  (Toldt,  Sitz.-ber.  Akad.  d. 
Wiss.  Wien,  1881,  vol.  82,  pp.  57-128). 

The  pits  are  often  described  as  if  they  were  epithelial  depressions  sepa- 
rate from  the  glands,  since  the  same  sort  of  epithelium  which  lines  them  is 
found  on  the  free  surface.  Developmentally,  however,  they  are  to  be  re- 
garded as  parts  of  the  glands,  comparable  with  ducts.  The  epithelial  cells 
of  the  pits  (Fig.  245)  consist  of  a  basal  protoplasmic  portion  containing  elon- 
gated, round,  or  sometimes  flattened  nuclei,  and  an  outer  portion  contain- 
ing the  centrosome  and  secretion.  The  mass  of  mucus  may  cause  the  thin 
top  plate  to  bulge,  and  in  preserved  tissue  to  rupture,  but  this  may  be  due 
to  reagents.  The  mucus  first  appears  in  granular  form. 

The  gastric  tubules  are  straight  or  somewhat  tortuous  slender  struc- 
tures, with  narrow  lumens.  The  portion  which  joins  the  pit  constitutes 


254 


HISTOLOGY 


the  neck  of  the  gland,  and  the  slightly  expanded  basal  end  is  the  fundus. 
Apparently  the  neck  is  the  zone  of  growth,  since  it  is  the  place  where 


Epithelium. 


Tunica  propria. 


Parietal  cells. 


Chief  cells. 


Leucocytes.  _ 


Smooth  muscle  fibers. 


Gastric  pit. 


Neck. 


Tubules 
of  the 
gastric 
glands. 


Parietal  cell. 


PIG.  245. — VERTICAL  SECTION  iOF  THE  Mucous  MEMBRANE  OF  A  HUMAN  STOMACH,  SHOWING  GASTRIC 
GLANDS  (GLANDULE  GASTRIOE  PROPRLS).     X  220. 

mitotic  figures  are  found.     Each  tubule  is  composed  of  cells  of  two  sorts, 
chief  cells  and  parietal  cells. 

The  chief  cells  usually  form  the  greater  part  of  the  tubules.     They  are 


STOMACH 


255 


Gland  lumen. 


FlG.  246. T  RANSVERSE    SECTION  OF  L  A 

HUMAN  GASTRIC  GLAND.     X  240. 


Axial  lumen. 


Parietal  cells  with 
intracellular  se- 
cretory capillar- 
ies 


wedge-shaped  cells,  having  a  narrow  contact  with  the  lumen;     In  general 

they  have  the  aspect  of  serous  cells,  containing  round  nuclei  and  granular 

protoplasm.     The  granules,  which  are  coarser  toward  the  lumen,  do  not 

respond  to  mucin  stains.     They  accumulate,  and  the  chief  cells  enlarge,  in 

the  absence  of  food  from  the  stomach;  but 

during  gastric  digestion,  the  cells  become  *»^-     Chief  ceil. 

small  and  the  granules  disappear.      They    Parietal  ceil. 

apparently  give  rise  to  the  pepsin  of  the 

gastric    juice,    and    are    called   zymogen 

granules.      After    death    the    chief    cells 

rapidly  disintegrate,  and  the  granules  are  seldom  well  preserved  except  in 

special  preparations. 

The  parietal  cells,  even  in  fresh  tissue,  may  be  readily  distinguished 
from  the  chief  cells;  the  latter  are  dark  and  contain  refractive  granules, 

whereas  •  the  parietal  cells  are  clear. 
They  are  large  cells,  containing  one  or 
occasionally  two  round  nuclei,  and  are 
crowded  away  from  the  lumen  like  the 
cells  in  the  serous  crescents  (Figs.  245 
and  246).  They  discharge  their  secre- 
tion through  secretory  capillaries  which 
produce  basket-like  networks  within 
the  protoplasm;  thus  they  differ  from 
the  chief  cells  which  have  only  inter- 
cellular secretory  capillaries.  The 
secretory  capillaries  of  the  parietal  cells 
may  be  demonstrated  by  the  Golgi 
method,  which  produces  a  precipitate 
wherever  secretion  is  encountered  (Fig. 
247).  After  fasting,  the  parietal  cells 
are  small  and  their  intracellular  capil- 
laries have  disappeared.  Following 
abundant  meals,  these  cells  enlarge  and 
may  contain  vacuoles  due  to  the  rapid 
formation  of  secretion.  They  produce 
the  hydrochloric  acid  which  is  found  in 
the  gastric  juice. 

In  ordinary  preparations  they  are 
better  preserved  than  the  chief  cells,  and  exhibit  a  finely  granular  structure, 
being  deeply  stained  with  the  anilin  protoplasmic  dyes.  They  differ  so 
markedly  from  the  chief  cells  that  they  have  been  erroneously  believed  to 
develop  from  the  surrounding  tunica  propria.  As  seen  in  Fig.  245  they 
occur  chiefly  along  the  body  of  the  tubule,  being  infrequent  at  its  fundus. 


Intercellular  secre- 
tory capillaries. 


Chief  cells/ 


FIG.  247. — GOLGI  PREPARATION,  SHOWING  THE 
SECRETORY  CAPILLARIES  IN  GASTRIC 
GLANDS.  X  230. 


256 


HISTOLOGY 


The  pyloric  glands  are  found  near  the  pylorus,  but  the  area  which  they 
occupy  is  not  sharply  set  off;  they  pass  over  into  gastric  glands  through 
a  "transition  zone."  Pyloric  glands  have  very  deep  pits,  from  which 
short,  winding,  branched  tubules  grow  out.  Their  form  in  the  adult  is 
shown  in  Fig.  248.  The  cells  in  the  pits  are  mucous  cells,  and  those  in 

Gastric  pits. 


Simple  epithelium 
cut  obliquely,  so 
that  it  appears  to 
be  stratified. 


•  Tunica  propria. 


;£•: 


•Pyloric  gland. 


^ections  of  pyloric 
glands. 


Solitary  nodule. 


,  Muscularis 
mucosae. 


FIG.  248. — VERTICAL  SECTION  OF  HUMAN  PYLORIC  GLANDS.     X  90. 

the  tubules  are  also  regarded  as  mucous  cells.  The  latter  are  columnar, 
with  rounded  nuclei  in  their  basal  part,  and  protoplasm  which  may  closely 
resemble  that  of  the  chief  cells.  Parietal  cells  are  occasionally  found,  and 
such  cells  have  been  reported  in  the  duodenal  glands  and  in  the  superficial 
glands  of  the  oesophagus.  Slender  dark  cells,  apparently  due  to  com- 


STOMACH 


257 


Mucosa. 


Muscularis 


pression,  are  found  in  the  pyloric  glands  of  the  dog.     In  certain  respects 
the  pyloric  glands  are  transitional  between  gastric  and  duodenal  glands. 

'The  tunica  propria  consists  of  the  small  amount  of  reticular  and  connect- 
ive tissue  which  is  found  between  the  closely  packed  glands  and  immedi- 
ately beneath  them  (Fig.  249).  It  is  sufficient  to  support  the  numerous 
capillaries  branching  about  the  glands,  the  terminal  lymphatic  vessels 
and  nerves,  numerous  wandering  cells  and  a  few  vertical  smooth  muscle 
fibers  prolonged  from  the  muscularis  mucosae  (Fig.  245).  The  lymphatic 
vessels  begin  blindly 
near  the  superficial  epi- 
thelium and  pass  be- 
tween the  glands  into 
the  submucosa  where 
they  spread  out  and 
are  easily  seen;  they 
continue  across  the 
muscularis  and  pass 
through  the  mesentery 
to  join  the  large  lym- 
phatic trunks..  Solitary 
nodules  occur  in  the 
gastric  mucosa,  espe- 
cially in  the  cardiac  and 
pyloric  regions  (Figs. 
243  and  248) ;  they  may 
extend  through  the 
muscularis  mucosae  into 
the  submucosa.  The 
muscularis  mucosae  may 
be  divided  into  two  or  three  layers  of  fibers  having  different  directions. 
The  submucosa  contains  its  plexus  of  nerves  and  many  vessels,  together 
with  groups  of  fat  cells.  Its  elastic  fibers  are  said  to  be  abundant  toward 
the  pylorus. 

The  muscular  coat  of  the  stomach  consists  of  three  layers  of  smooth 
muscle,  an  outer  longitudinal,  middle  circular,  and  inner  oblique  layer 
respectively.  Tliese  layers  can  be  recognized  by  dissection  more  readily 
than  by  microscopic  examination,  and  were  found  by  Willis  in  1674. 
The  middle  layer  is  the  one  most  highly  developed.  It  not  only  sur- 
rounds the  body  of  the  stomach,  but  as  the  fundus  pushes  outward, 
muscle  fibers  of  this  layer  encircle  its  apex  concentrically.  Toward  the 
pylorus,  along  the  antrum,  the  circular  layer  gradually  thickens,  thus 
forming  the  sphincter  pylori;  it  becomes  abruptly  thin  in  the  duodenum. 
There  is  no  sphincter  at  the  cardia,  where  the  circular  layer  is  continuous 
17 


Epithelium. 


Tunica  propria. 


Muscularis  mucosae.    ^ 


Submucosa. 


Smooth  muscle  cut 
lengthwise. 


Connective  tissue. 


Smooth  muscle  cut 
transversely. 


Serosa. 

FIG.  249. — VERTICAL  SECTION  OF  THE  WALL  OF  A  HUMAN  STOMACH. 
The  tunica  propria  contains  glands  standing  so  close  together  that 

its  tissue  is  visible  only  at  the  base  of  the  glands  toward  the 

muscularis  mucosas. 


HISTOLOGY 

with  that  of  the  oesophagus,  but  elastic  tissue  in  the  muscularis  is  said  to 
be  specially  abundant  and  to  "contribute  to  the  tonus  of  the  cardiac  mus- 
culature." The  outer  longitudinal  layer,  continuous  with  the  outer  layer 
in  the  oesophagus  and  duodenum,  is  an  incomplete  layer,  being  deficient 
toward  the  greater  curvature.  As  the  body  of  the  stomach  bulges  out- 
ward to  form  this  curvature,  the  longitudinal  fibers  apparently  become 
separated  into  scattered  bundles.  In  the  pars  pylorica,  however,  there 
is  a  continuous  longitudinal  layer,  and  some  of  its  fibers,  which  become 
intermingled  with  those  of  the  sphincter  pylori,  serve  to  dilate  the  py- 
lorus. The  innermost  layer,  composed  of  oblique  fibers,  is  not  represented 

in  the  oesophagus  and  duodenum, 
and  is  said  to  be  absent  from  the 
pars  pylorica.  The  peculiar  arrange- 
ment of  its  fibers  is  shown  in  Fig. 
250,  in  which  the  outer  longitudinal 
layer  has  been  almost  entirely  re- 
moved, and  windows  have  been  cut 
through  the  circular  layer;  the  oblique 
fibers  are  seen  against  the  submucosa. 

&I/  WT/sZPM^  *y  They  form  a  longitudinal  strand  par- 

allel  with  the  lesser  curvature,  and 
they  pass  from  one  side  of  the 

FIG  250. — A  DISSECTION  OF  THE  MUSCULATURE  ,    i    ^      4.1      ^+.1,^  ,„  ^-V,^    >^<-^V, 

OF  THE  STOMACH.  (Spaitehoiz.)  stomach  to  the  other  across  the  notch 

a  and  e,   Longitudinal  layer;  b  and  d,  circular        K/at-rarApm    fViA    rpcrn^l-iQ  mic  anrl   fiinrhiQ 
layer;  c,  oblique  layer;  Py.,  pylorus;   S    I.,        DCtWCen   Uie    CCSOpnagUS  and  lUndUS. 

These   fibers  are  important  in  the 

activity  of  the  gastric  canal,  but  they  do  not  produce  the  canal  as  some 
have  supposed.  From  these  longitudinal  bundles,  fibers  curve  obliquely 
toward  the  greater  curvature,  where,  as  transverse  fibers  they  cross  to 
the  opposite  side.  Thus  the  musculature  of  the  stomach  is  so  arranged 
that  it  is  very  difficult  to  determine  the  plane  of  section  in  a  small  piece 
of  gastric  mucous  membrane,  which  is  usually  cut  obliquely;  but  the 
section  shown  in  Fig.  249,  with  inner  and  outer  layers  cut  lengthwise 
and  a  middle  layer  cut  across,  is  consistent  with  a  longitudinal  section 
of  the  corpus  gastri. 

The  tunica  serosa  consists  of  connective  tissue  with  well-developed  elas- 
tic nets,  and  a  covering  of  peritoneal  epithelium  interrupted  only  along 
the  curvatures,  at  the  mesenteric  attachments.  It  contains  the  nerves  and 
vessels  which  supply  the  stomach.  The  right  and  left  vagus  trunks  de- 
scend beside  the  oesophagus  as  the  main  stems  in  a  plexiform  network, 
and  then  come  together  along  the  lesser  curvature.  From  there  they 
send  plexiform  branches  over  both  sides  of  the  stomach,  and  the  main 
stems  continue  into  the  small  intestine.  Sympathetic  nerves  from  the 
cceliac  plexus  pass  to  the  pyloric  end  of  the  stomach  and  join  the  vagus 


DUODENUM 


259 


plexus.     The  further  distribution  of  the  nerves  in  myenteric  and   sub- 
mucous  plexuses  is  similar  to  that  in  the  small  intestine. 

DUODENUM. 

The  duodenum  contains  branched  mucous  glands,  the  bodies  of  which 
are  found  in  the  submucosa.     These  are  called  duodenal  glands  (Brunner's 


Intestinal  glands 
Epithelium.      Villi. 


Duodenal  gland. 
Plica  circularis. 


Duodenal  glands  in  the 
submucosa. 


Oblique 

section. 

I 


Intestinal  glands 


Transverse 
section. 


Tunica  propria. 

Muscularis 

mucosae. 
Submucosa.— p 

Stratum  of 
circular  muscle. 

Stratum  of  longi-_f 
tudinal  muscle,      i 

Connective  tissue — »„   . - 

FIG.  251. — LONGITUDINAL  SECTION  OF  THE  HUMAN  DUODENUM. 

glands)  and  they  occur  nowhere  else  in  the  small  intestine  (Fig.  251). 
Their  cells  produce  a  mucus  which  stains  with  difficulty,  thus  contrasting 
with  the  mucus  of  the  goblet  cells  in  the 
tubular  glands  above  them.  The  nature 
of  their  epithelium  is  shown  in  Fig.  252, 
which  shows  also  that  a  portion  of  their 
tubules  may  lie  above  the  muscularis 
mucosae,  in  the  tunica  propria.  As  in  the 
pyloric  glands,  occasional  parietal  cells 
have  been  found,  and  also  the  dark  cells, 
due  to  compression.  Secretory  capillaries 
extend  out  from  the  lumen  between  the 
cells,  and  the  tubules  are  provided  with  a 
structureless  basement  membrane.  The 
ducts  of  the  duodenal  glands  may  open 
on  the  free  surface  of  the  epithelium,  or 
into  the  lower  ends  of  the  tubular  pits 
situated  in  the  mucous  membrane  and 
known  as  intestinal  glands.  The  duodenal 
glands  are  so  numerous  toward  the  stom- 
ach that  the  submucosa  may  be  filled 
with  their  tubules.  They  are  also  abun- 
dant near  the  duodenal  papilla  where  the 


Oblique 
section. 


Longitudinal 
section. 


of  the  tubules  of  a  duodenal  gland. 

FIG.  252. — FROM  A  SECTION  OF  A  HUMAN 

DUODENUM.     X  240. 
Only  the  lower  half  of  the  mucosa  and 

upper    half     of    the    submucosa    are 

sketched. 


260 


HISTOLOGY 


bile  and  pancreatic  ducts  enter  the  descending  portion  of  the  duodenum. 
Beyond  this  point  they  become  fewer,  and  disappear  before  the  end  of 
the  duodenum  is  reached.  Except  for  these  glands  the  duodenum  is 
essentially  like  the  remainder  of  the  small  intestine,  described  in  the 
following  section. 


JEJUNUM  AND  ILEUM. 

The  lining  of  the  small  intestine,  including  the  duodenum,  has  a  velvety 
appearance,  due  to  the  presence  of  innumerable  cylindrical,  club-shaped 
or  foliate  elevations,  known  as  mill  (hairs  or  nap).  True  yilli  are  found 
in  the  large  intestine  of  the  embryo  but  they  disappear  before  birth;  they 
are  said  to  occur  also  in  the  pyloric  end  of  the  stomach,  but  it  is  question- 
able whether  these  are  typical  villi  or  merely  irregular  folds.  Elsewhere 
in  the  digestive  tube,  villi  are  absent.  At  the  bases  of  the  villi  there  are 
simple  tubular  pits  of  glandular  epithelium,  which  extend  to  the  muscu- 
laris  mucosae  but  do  not  penetrate  it;  these  are  the  intestinal  glands  (glandu- 
les intestinales ',  formerly  known  as  crypts  of  Lieberkuhn).  An  enlarged 


FIG.  253. 

A,  Surface  view  of  the  hardened  mticosa  of  the  small  intestine  (after  Koelliker).     B,rSide  view  of  a  wax 
reconstruction  of  the  epithelium  in  the  human  duodenum  (Huber).     i.  g.,  Intestinal  gland;  v.,  villus. 

surface  view  of  the  hardened  mucous  membrane  is  shown  in  Fig.  253,  A. 
The  orifices  of  the  glands  appear  as  round  holes;  the  villi,  which  are  from 
0.2-1.0  mm.  in  height,  have  fallen  over  in  various  directions.  Within 
the  duodenum  the  villi  are  low  leaf -like  folds,  0.2-0.5  mm.  high,  seen  in 
side  view  in  the  reconstruction,  Fig.  253,  B.  Their  shape  cannot  be  deter- 
mined from  inspecting  single  sections  (cf.  Fig.  251). 

It  will  be  seen  that  villi  are  essentially  circumscribed  folds,  and  they 
have  been  said  to  arise  through  the  subdivision  of  longitudinal  ridges 
(Berry,  Anat.  Anz.,  1900,  vol.  17,  pp.  242-249).  According  to  Johnson 
(Amer.  Journ.  Anat.,  1910,  vol.  10,  pp.  521-561)  they  develop  as  low 
knob-like  elevations  which  increase  in  height.  They  may  become  sub- 
divided, as  indicated  by  bifid  villi  (Fig.  253). 

The  small  intestine  contains  other  elevations  of  its  lining  which  are 
much  larger  than  the  villi.  These  are  the  circular  folds  (plica  circulares, 


SMALL    INTESTINE 


26l 


formerly  known  as  Kerkring's  valvula  conniventes) ,  which  are  seen  con- 
spicuously on  opening  the  intestine.  They  are  thin  leaf-like  membranes, 
in  places  very  close  together,  which,  as  their  name  implies,  tend  to  encircle 
the  tube.  Sometimes  they  form  short  spirals,  and  they  may  branch  and 
connect  with  one  another.  They  begin  in  the  duodenum,  and  beyond  the 
duodenal  papilla  they  are  tall  and  close  together.  They  are  highly 
developed  in  the  jejunum  and  form  its  most  characteristic  feature.  In 
the  ileum  they  are  lower  and  further  apart;  and  they  may  come  to  an 
end  two  feet  above  the  colon.  The  villi  correspondingly  are  taller  and 


Villi. 


X  X 


Plica  circularis. 


Intestinal  glands. 


Epithelium. 


Tunica 
\  propria. 


Submucosa. 


Submucosa.  -• 


Circular  muscle.  \i 

Longitudinal 
muscle. 

Serosa  ^"~" 


•'    Plexus 

.    _^- ~-~"  myen- 
^Cpfe;      tericus. 


PIG.  254. — VERTICAL  LONGITUDINAL  SECTION  OF  THE  JEJUNUM  OF  AN  ADULT  MAN.  X  16. 
The  plica  circularis  on  the  right  supports  two  small  solitary  nodules,  which  do  not  extend  into  the  sub- 
mucosa;  one  of  them  exhibits  a  germinal  center,  x.  The  epithelium  is  slightly  loosenedffrom  the 
connective  tissue  core  of  many  of  the  villi,  so  that  a  clear  space,  xx,  exists  between  the  two.  The 
isolated  bodies  lying  near  the  villi  (more  numerous  to  the  left  of  the  plicae  circulares)  are^sections  of 
villi  that  were  bent,  so  that  their  ends  were  cut  off  in  sectioning. 


more  numerous  in  the  jejunum  than  in  the  ileum,  in  the  distal  part  of  which 
they  are  short  and  scattered,  finally  disappearing  on  the  colic  surface  of 
the  valve  of  the  colon  (ileo-caecal  valve).  Thus  few  and  short  villi  and 
scattered  plicae  indicate  that  a  section  of  the  intestine  is  from  the  ileum. 

As  seen  in  sections,  the  plica  circulares  are  elevations  of  the  sub- 
mucosa  (Fig.  254)  covered  on  both  sides  by  the  entire  mucous  membrane 
— villi,  glands  and  the  muscularis  mucosae.  A  low  plica  of  the  duodenum 
is  shown  in  Fig.  251. 


262 


HISTOLOGY 


The  glands,  villi,  and  plicae  have  usually  been  regarded  as  permanent  structures, 
serving  to  increase  the  secreting  and  absorbing  surfaces  of  the  intestine.  In  mammals 
they  apparently  are  not  obliterated  by  the  normal  distention  of  the  intestine,  although 
the  villi  may  become  shorter,  the  glands  shallower,  and  the  plicae  may  be  partially 
taken  up  like  the  folds  of  the  oesophagus.  In  the  guinea-pig,  and  to  some  extent  in 
the  rabbit  and  cat,  Heitzmann  found  that  the  villi  change  their  shape  with  the  intes- 


FIG.  255. — EFFECTS  OF  DISTENTION  ON  THE  SMALL  INTESTINE  OF  THE  ADULT  GUINEA-PIG.     X  so. 

(Johnson.) 
A,  Strongly  contracted;  B,  normally  distended  with  food;  C,  distended  with  a  pressure  of  150  cm.  of  water. 


tinal  contractions  and  expansions  associated  with  its  physiological  activity.  Johnson 
(Amer.  Journ.  Anat.,  1913,  vol.  14,  pp.  235-250)  has  shown  that  in  guinea-pigs  the 
villi  and  glands  of  the  contracted  intestine  have  the  form  seen  in  Fig.  255,  A;  with  nor- 
mal distention  due  to  abundant  food,  they  appear  as  in  B ;  and  with  extreme  artificial 
distention,  the  glands  and  villi  are  nearly  obliterated  as  in  C.  The  tube  expands 
to  this  limit,  beyond  which  additional  pressure  has  no  effect  until  it  ruptures.  On 
releasing  the  pressure,  glands  and  villi  return  to  their  normal  size.  Interesting  ques- 
tions are  suggested,  as  to  how  the  muscle  fibers  become  rearranged  in  the  thin  layer 
when  the  intestine  is  distended,  and  what  takes  place  in  the  blood  and  lymphatic  vessels. 
These  problems  are  under  investigation. 

Finer  Structure  of  the  Glands  and  Villi.  At  the  blind  lower  end  or 
fundus  of  the  glands,  there  occur  certain  cells  containing  many  coarse 
granules  in  that  part  of  their  protoplasm  which  is  toward  the  lumen  (Fig. 
256).  These  cells  were  first  described  by  Paneth  (Arch.  f.  mikr.  Anat., 
1888,  vol.  31,  pp.  113-191)  and  are  known  as  Paneth' s  cells.  They  are 
found  in  the  glands  of  the  duodenum,  jejunum  and  ileum,  but  not  in  those 
of  the  large  intestine.  Although  they  may  be  observed  with  ordinary 
stains,  they  are  more  strikingly  demonstrated  in  iron-haematoxylin  prepara- 
tions. Apparently  they  produce  a  special  secretion,  which  enters  the 
lumen  of  the  gland  in  the  form  of  fine  granules  when  the  digestion  of  fat 


SMALL   INTESTINE 


263 


is  taking  place,  and  may  perhaps  be  concerned  also  with  protein  digestion, 
but  not  with  that  of  carbohy- 
drates (Miram,  Arch.  f.  mikr. 
Anat.,  1912,  vol.  79,  pp.  105- 
113).  They  do  not  contain 
mucinogen  granules,  although 
goblet  cells  occur  in  their  im- 
mediate vicinity. 

A  short  distance  above  the 
fundus,  the  epithelial  cells  of 
the  glands  exhibit  mitotic  fig- 
ures. From  this  it  is  inferred 
that  the  outer  cells,  including 
those  of  the  villi,  are  renewed 
from  below.  The  cells  near  the 
bottom  of  the  gland  have 
terminal  bars,  but  they  are  not 
as  distinct  as  those  of  the  villi. 


b  _ 


FIG.  256. — THE  FUNDUS  OF  AN  INTESTINAL  GLAND  FROM 

THE  DUODENUM  OF  A  GUINEA-PIG.     X  480. 

a,  Cell   in    mitosis;    b,  lymphocyte;    c,  Paneth's  cell; 

d,  goblet  cell. 

During  division,  the  cell  seems  to  be 


drawn  up  from  the  basement  membrane,  as  if  held  in  position  by  the 


Epithelium. 


~  Tunica  propria. 


Portion  of  a  capillary 
&  blood  vessel. 


Cuticula. 


Nucleus   of  a  lympho- 
cyte. 


Tangential  section  of  a 
goblet  cell. 


Mucus  in  a  goblet  cell. 


Nucleus  of  a  smooth  muscle  fiber.  Central  lymphatic  vessel. 

FIG.  257. — LONGITUDINAL  SECTION  THROUGH  THE  APEX  OF  THE  VILLUS  OF  A  DOG.     X  360. 
The  goblet  cells  contain  less  mucus  as  they  approach  the  summit  of  the  villus. 

terminal  bars  (Fig.  256,  a).     The  plane  of  division  is  at  right  angles  with 
the  long  axis  of  the  gland  (as  shown  on  the  right  of  Fig.  256),  and  after 


264 


HISTOLOGY 


Epithelium. 


FIG.  258. — FROM  A  SECTION  OF  THE  SMALL  INTESTINE  FROM 

ASKITTEN  SEVEN  DAYS  OLD.     X  250. 
The    epithelium    on    the    left    contains    many    wandering 

leucocytes  (lymphocytes).     The  epithelium  on  the  right 

contains  but  three. 


mitosis  the  nuclei  move  back  to  the  basal  layer.  Lymphocytes  which 
have  made  their  way  between  the  epithelial  cells  (Fig.  256,  &),  are 
frequently  seen,  and  when  near  the  lumen  and  over-stained  they  may  be 
mistaken  for  mitotic  figures. 

The  sides  of  the  glands  and  surfaces  of  the  villi  are  covered  with  simple 
columnar  epithelium,  similar  to  that  shown  in  Fig.  256.  It  contains 
goblet  cells  separated  from  one  another  by  cells  free  from  mucus.  The 

cells  of  the  villi  are  taller  than 
those  in  the  glands,  and  the 
goblet  cells  are  somewhat 
larger,  but  toward  the  tip  of 
the  villus  they  become  slen- 
der and  empty  (Fig.  257). 
The  top  plates  or  cuticula 
become  thicker  from  the 
fundus  of  the  gland  outward 
to  the  tips  of  the  villi,  and 
when  well  developed  they 
exhibit  vertical  striations  which  are  considered  to  be  protoplasmic 
processes  lodged  in  pores.  The  top-plate  of  the  goblet  cells  is  thin  and 
apparently  ruptures  to  allow  the  escape  of  the  mucus.  Lymphocytes 
may  enter  the  epithelium  in  abundance  as  shown  in  Fig.  258. 

Interest  in  the  villi  centers  chiefly  in  their  relation  to  the  absorption 
of  nutritive  material  from  the  intestinal  contents  (chyme).  Fat,  chem- 
ically changed  so  that  it  does  not 


blacken  with  osmic  acid,  is  con- 
veyed through  the  cuticula. 
Within  the  epithelial  cells  it  forms 
characteristic  fat  droplets,  which 
appear  in  abundance  also  between 
the  epithelial  cells.  Lymphocytes 
ingest  the  droplets,  and  may  then 
enter  the  lymphatic  vessel  in  the 
central  axis  of  the  villus  (Fig. 
257),  but  apparently  fat  is  con- 
veyed to  the  lacteals  also  through  intercellular  spaces,  without  the  inter- 
vention of  leucocytes.  Within  the  lymphatic  vessel  it  forms  the  milky 
lymph  known  as  chyle. 

In  regard  to  the  absorption  of  protein  material,  the  observations  of  Pio  Mingazzini, 
which  have  been  confirmed  by  some  and  denied  by  others,  are  of  considerable  interest. 
As  shown  in  Fig.  259,  he  found  that  the  basal  protoplasm  of  the  resting  epithelium 
presented  an  ordinary  appearance  (A),  but  that  after  absorption  had  progressed,  hya- 
line spherules  appeared  in  it  (B).  As  these  became  numerous  they  were  detached  from 


B 


FIG.  259. — STAGES  OF  INTESTINAL  ABSORPTION  AS 
SEEN  IN  EPITHELIAL  CELLS  OF  VILLI  FROM  A 
HEN.  (After  Mingazzini.) 

A  and  D,  The  states  of  repose  preceding  and  follow- 
ing the  process,  s.,  Spherules. 


SMALL  INTESTINE 


265 


the  cells,  forming  a  reticular  mass  between  them. and  the  tunica  propria  (C).  After 
the  spherules  had  broken  down  and  had  probably  been  transferred  to  the  blood  vessels, 
the  tunica  propria  entered  into  its  usual  relation  with  the  shortened  epithelium  (D). 
The  basal  protoplasm  was  then  restored.  According  to  this  interpretation  protein 
absorption  is  accomplished  as  a  secretory  process  of  the  epithelium,  the  product  being 
eliminated  from  its  basal  portion.  The  spherules  accumulate  at  and  near  the  tips  of 
the  villi,  in  spaces  which  many  authorities  describe  as  due  to  the  artificial  retraction 
of  the  tunica  propria  (Fig.  260,  a).  The  spherules  have  been  considered  a  coagulum 
of  the  fluid  squeezed  from  the  reticular  tissue.  In  part  they  may  be  boundaries  of 
the  basal  ends  of  epithelial  cells  on  the  distal  wall  of  the  villus. 

Sections  of  villi.         a  b 


Ephitelium 


Tunica 
propria. 


Submucosa.    Intestinal  glands.  Oblique  sections  of  intestinal  glands. 

FIG.  260. — VERTICAL  SECTION  OF  THE  Mucous  MEMBRANE  OF  THE  JEJUNUM  OF  AN  ADULT  MAN.     X  80. 
The  space,  a^between  the  tunica  propria  and  the  epithelium  of  the  villus  is  perhaps  the  result  of  the  shrink. 

ing  action  of  the  fixing  fluid.     At  b  the  epithelium  has  been  artificially  ruptured.     The  goblet  cells 

have^been  drawn  on  one  side  of  the  villus  on  the  right. 


Outer  layers  of  the  small  intestine.  The  tunica  propria,  which  forms  the 
cores  of  the  villi  and  extends  between  the  glands,  is  a  reticular  tissue, 
containing  the  usual  types  of  free  cells  and  also  a  large  number  of  plasma 
cells  (see  p.  68).  Slender  strands  of  smooth  muscle  extend  up  and  down 
the  villi,  being  inserted  into  the  reticulum,  and  by  contraction  they  cause 
the  villi  to  shorten.  The  muscularis  mucoscB  consists  of  an  inner  circular 
and  an  outer  longitudinal  layer,  thus  duplicating  on  a  small  scale  the  tunica 
muscularis.  The  submucosa  is  a  connective  tissue  layer,  such  as  has  been 
described  in  the  stomach  and  oesophagus,  and  the  muscularis  is  divided  into 
a  thick  inner  circular  layer  of  smooth  muscle  and  a  thinner  outer  longitu- 
dinal layer,  between  which  is  a  thin  stratum  of  intermuscular  connective 


266 


HISTOLOGY 


tissue.     The  intestine  is  covered  externally  by  the  tunica  serosa.     The 
distribution  of  the  vessels  and  nerves  in  these  layers  is  as  follows. 

Blood  vessels.  The  arteries  pass  from  the  mesentery  into  the  serosa, 
in  which  their  main  branches  tend  to  encircle  the  intestine.  Smaller 
branches  from  these  pass  across  the  muscle  layers  to  the  submucosa,  in 
which  they  subdivide  freely  (Fig.  261,  A).  In  crossing  the  muscle  layers 
they  send  out  branches  in  the  intermuscular  connective  tissue.  These 
and  the  arteries  of  the  serosa  and  submucosa  supply  the  capillary  networks 
found  among  the  muscle  fibers.  The  capillaries  are  mostly  parallel  with 
the  muscles.  From  the  submucosa  the  arteries  invade  the  mucosa,  form- 


s.m. 


c.m. 
i.e. 


A  :B  c 

FIG.  261. 

A,  Diagram  of  the  blood  vessels  of  the  small  intestine;  the  arteries  appear  as  coarse  black  lines;  the  cap- 
illaries as  fine  ones,  and  the  veins  are  shaded  (after  Mall).  B,  Diagram  of  the  lymphatic  vessels  (atter 
Mall).  C,  Diagram  of  the  nerves,  based  upon  Golgi  preparations  (after  Cajal).  The  layers  of  the 
intestine  are  m.,  mucosa;  m.  m.,  muscularis  mucosse;  s.  m.,  submucosa;  c.  m.,  circular  muscle;  i.  c., 
intermuscular  connective  tissue;  1.  m.,  longitudinal  muscle;  s.,  serosa.  c.  1.,  central  lymphatic;  n., 
nodule;  s.  pi.,  submucous  plexus;  m.  pi.,  myenteric  plexus. 

ing  an. irregular  capillary  network  about  the  glands,  and  sending  larger 
terminal  branches  into  the  villi.  There  is  usually  a  single  artery  for  a 
villus,  and  it  has  been  described  as  near  the  center,  with  the  veins  at  the 
periphery  (Fig.  261),  or  sometimes  on  one  side  of  the  villus  with  the  vein 
on  the  other.  The  network  of  blood  vessels  in  the  villi  is  very  abundant 
as  shown  in  Fig.  262.  The  veins  branch  freely  in  the  submucosa  and  pass 
out  of  the  intestine  beside  the  arteries.  The  muscularis  mucosae  has  been 
described  as  forming  a  sphincter  for  the  veins  which  penetrate  it;  thus  it 
may  control  the  amount  of  blood  within  the  villi.  No  valves  occur 
until  the  veins  enter  the  tunica  muscularis;  there  they  appear,  and  con- 
tinue into  the  collecting  veins  in  the  mesentery.  They  are  absent  from 


SMALL   INTESTINE 


267 


the  large  branches  of  .the  portal  vein  which  receive  the  blood  from  the 
intestines. 

Lymphatic    vessels.     The  intestinal  lymphatics   (lacteals)   appear  as 


Vein. 


Tunica  propria.  — tJ 


I 

Muscularis  mucosae.  Submucosa. 

FIG.  262. — VERTICAL  SECTION  OF  THE  Mucous  MEMBRANE  OF  THE  HUMAN  JEJUNUM.     X  so. 
The  blood  vessels  are  injected  with  Berlin  blue.     The  vein  of  the  first  villus  on  the  left  is  cut  transversely. 


Villus. 


Intestinal  glands. 


Submucosa. 


Muscularis 
mucosae.        Lymph  nodules. 


Circular        Longitudinal 
layer.  layer. 


of  the  muscularis. 

FIG.  263. — TRANSVERSE  SECTION  OF  AGGREGATE  NODULES  OF  THE  SMALL  INTESTINE  OF  A  CAT. 
The  crests  of  four  nodules  were  not  within  the  plane  of  the  section.     X  10. 

central  vessels,  within  the  villi  (Fig.  261,  B).  Each  villus  usually  contains 
a  single  lacteal  ending  in  a  blind  dilatation;  sometimes  there  are  two  or 
three  which  form  terminal  loops.  In  some  stages  of  digestion  the  disten- 


268 


HISTOLOGY 


tion  of  these  lymphatics  is  very  great  and  their  endothelium  is  easily 
seen  in  sections.  When  collapsed  they  are  hard  to  distinguish  from  the 
surrounding  reticulum.  Small  lateral  branches  and  a  spiral  prolongation 
of  the  central  lymphatic  have  been  found  by  injection,  but  these  may  be 
tissue  spaces  into  which  the  injected  fluid  has  been  forced.  The  lym- 
phatics branch  freely  in  the  submucosa  and  have  numerous  valves.  They 
cross  the  muscle  layers,  spreading  in  the  intermuscular  tissue  and  the  serosa, 
and  pass  through  the  mesentery  to  the  thoracic  duct. 

Lymphoid  tissue.  The  lymphoid  tissue  of  the  intestine  occurs  pri- 
marily in  the  tunica  propria,  and  in  three  forms — diffuse  lymphoid  tissue, 
solitary  nodules,  and  aggregate  nodules.  Solitary  nodules  are  seen  in  Fig. 
254.  The  nodules  are  surrounded  by  small  vessels,  the  lymphatics  being 


B 


FIG.  264. 

A,  Surface  view  of  the  plexus  myentericus  of  an  infant.  X  SO.  g.  Groups  of  nerve  cells;  r,  layer  of  cir- 
cular muscle  fibers  recognized  by  their  rod-shaped  nuclei.  B,  Surface  view  of  the  plexus  submucosus 
of  the  same  infant.  X  50.  g,  Groups  of  nerve  cells;  b,  blood  vessel  visible  through  the  overlying 
tissue. 

drawn  in  Fig.  261,  B.  Blood  vessels  may  make  a  similar  net,  and  pene- 
trate the  outer  portion  of  the  nodule.  The  germinative  centers  are  simi- 
lar to  those  in  the  lymph  glands. 

Aggregate  nodules  (Peyer's  patches)  are  oval  areas,  usually  from  i  to 
4  cm.  long  but  occasionally  much  larger,  composed  of  from  ten  to  sixty 
nodules  in  close  contact  (Fig.  263).  The  nodules  may  be  distinct  or 
blended  in  a  single  mass.  They  distort  the  intestinal  glands  with  which 
they  are  in  relation,  and  immediately  above  the  nodules  the  villi  are  partly 
or  wholly  obliterated.  Thus  they  appear  as  dull  patches  in  the  lining 
of  the  freshly  opened  intestine,  and  may  be  readily  seen.  There  are  from 
fifteen  to  thirty  of  them  in  the  human  intestine  (rarely  as  many  as  fifty 
or  sixty)  and  they  occur  chiefly  in  the  lower  part  or  the  ileum  on  the  side 


SMALL   INTESTINE 


269 


opposite  the  mesentery.  A  few  occur  in  the  jejunum  and  the  distal  part 
of  the  duodenum.  In  the  vermiform  process,  diffuse  aggregate  nodules  are 
always  present,  but  they  do  not  occur  elsewhere  in  the  large  intestine. 

Nerves.  The  small  intestine  is  supplied  by  prolongations  of  the  vagus 
nerves,  which  are  joined  by  branches  of  the  superior  mesenteric  plexus 
of  the  sympathetic  System.  The  latter  are  regarded  as  the  principal 
supply.  This  plexus  is  ventral  to  the  a6rta,  and  sends  branches  through 
the  mesentery  into  the  serosa.  The  manner  in  which  they  penetrate  the 
other  layers,  forming  the  myenteric  plexus  (Auerbach's  plexus)  between 
the  circular  and  longitudinal  muscle-layers,  and  the  submucous  plexus 
(Meissner's  plexus)  in  the  submucosa,  is  shown  in  Fig.  261,  C.  In  surface 
view,  obtained  by  stripping  the  layers  apart,  these  plexuses  are  seen  in 
Fig.  264.  Their  branches  supply  the  smooth  muscle  fibers.  From  the 
submucous  plexus  the  nerves  extend  into  the  villi,  where  nerve  cells  have 
been  detected  by  the  Golgi  method  (Fig.  261,  C);  it  has  been  suspected, 
however,  that  some  of  these  " nerve  cells"  are  portions  of  the  reticular 
tissue.  The  nerve  fibers  probably  terminate  in  contact  with  epithelial 
cells  and  provide  for  local  reflex  action,  whereby  the  muscles  contract  in" 
response  to  stimulation  of  the  epithelium.  Most  of  the  intestinal  nerves 
are  non-medullated,  but  they  include  a  few  large  medullated  fibers  said 
to  have  free  endings  in  the  epithelium. 


MESENTERY  AND  PERITONEUM. 

The  serous  membrane  which  surrounds  the  intestinal  tube  and  certain 
other  abdominal  viscera  is  a  part  of  the  lining  of  the  body  cavity.  Its 
general  relations  are  shown  in  the  diagram,  Fig. 
265.  After  covering  the  ventral  surface  and  the 
sides  of  the  intestinal  tube,  the  two  layers  of  serous 
membrane  come  together  to  form  the  mesentery 
and  extend  to  the  dorsal  body  wall;  then,  separat- 
ing, they  pass  laterally  as  the  lining  of  the  abdom- 
inal walls  and  again  come  together  in  the  mid- 
ventral  line.  This  serous  membrane,  or  periton- 
eum, consequently  forms  a  closed  sac.  It  is  divis- 
ible into  the  visceral  peritoneum  which  covers  the 
viscera,  and  parietal  peritoneum  which  lines  the 
body  walls.  In  all  cases  its  free  surface  is  covered 
with  a  single  layer  of  flat  polygonal  cells,  resem- 
bling ehdothelium  (Fig.  266,  B).  Although  quite 
flat,  the  cells  have  a  thin  cuticular  border  which 

is  said  to  be  striated,  and  the  cuticulae  of  adjacent  cells  fit  together  closely. 
The  lateral  walls  of  these  flat  cells  are  connected  with  one  another  by  proto- 


FIG.  265. — DIAGRAM  OF  A 
MESENTERY  AS  SEEN  IN 
CROSS  SECTION  OF  THE 
ABDOMEN.  (After  Minot.) 

a.,  Aorta;  c.  p.,  cavity  of  the 
peritoneum;  int.,  intes- 
tine; mes.,  mesentery;  p. 
m.  and  v.  m.,  parietal  and 
visceral  layers  of  meso- 
thelium. 


270  HISTOLOGY 

plasmic  bridges;  thus  in  passing  through  the  epithelium  along  the  inter- 
cellular boundaries,  one  or  two  intercellular  vacuoles  would  be  encountered 
(Fig.  266,  A).  Wandering  cells  pass  readily  across  this  epithelium, 
between  the  cells,  and  substances  in  the  peritoneal  cavity  are  taken  up 
into  the  subserous  lymphatics.  It  has  long  been  thought  that  there  are 
permanent  orifices  or  "stomata"  between  the  epithelial  cells  (Fig.  266,  B); 
bounded  either  by  modified  protoplasm  or  by  separate  small  cells,  and  that 
lymphatic  vessels  open  directly  into  the  serous  cavity  through  such  sto- 
mata. This  is  contrary  to  recent  investigations  of  the  nature  of  lymphatic 

vessels,  and  the  existence  of  sto- 
mata as  permanent  apertures  has 
been  denied.  The  stomata,  so  fre- 
quently found  in  a  great  variety  of 
animals  may  be  shrinkage  effects 
caused  by  reagents,  but  their  in- 
terpretation is  not  clear.  In  any 
case,  the  transfer  of  material 
through  the  epithelium  takes  place 
readily,  and  the  substances  or  cells 
FIG.  266.-SEROUS  MEMBRANES.  which  pass  through  may  be  taken 

A,  Vertical  section  of  the  epithelium  (after  Heiden- 

(kaftner  LutriS).  '?**  ™*'  showing  two  stomata    up  freely  by  the  closed  lymphatic 


vessels  in  the  underlying  tissue. 
In  the  mesentery,  a  thin  layer  of  connective  tissue  with  elastic  networks 
and  interwoven  bundles  of  white  fibers  fills  the  interval  between  the  two 
epithelial  layers.  In  this  connective  tissue  there  are  many  lymphatic 
and  blood  vessels,  and  nerves  to  the  various  organs.  Mast  cells  may  be 
found  along  the  vessels,  especially  in  young  animals  (Fig.  55,  p.  68)  and 
various  other  forms  of  wandering  cells  occur.  The  connective  tissue  layer 
is  denser  in  the  parietal  than  in  the  visceral  peritoneum.  In  places  where 
the  peritoneum  is  freely  movable  there  is  a  subserous  layer  of  loose  fatty 
tissue,  but  there  is  no  subserous  layer  in  the  intestine. 

VERMIFORM  PROCESS. 


The  vermiform  process  is  a  "worm-like"  prolongation  of  the  caecum. 
Although  small  in  size,  in  structure  it  more  closely  resembles  the  large 
intestine,  of  which  it  is  a  part,  than  the  small  intestine.  In  embryos  of 
three  and  one-half  to  five  months  it  is  lined  with  villi,  but  with  further 
development  the  villi  flatten  out  and  disappear.  Meanwhile  the  glands, 
which  are  of  the  same  type  in  both  small  and  large  intestines,  have  devel- 
oped and  are  increasing  in  number  and  in  length.  Sometimes  they  pene- 


VERMIFORM  PROCESS 


271 


trate  the  muscularis  mucosae.  In  the  adult  (Fig.  267)  they  are  simple 
tubes,  occasionally  forked,  thus  indicating  the  way  in  which  they  multiply 
in  the  embryo.  As  early  as  the  fourth  month,  lymphoid  tissue  has  been 
found  in  the  vermiform  process,  and  at  birth  the  lymphoid  nodules  in  the 
tunica  propria  are  abundant  and  more  or  less  confluent.  The  great  devel- 
opment of  lymphoid  tissue  is  the  most  important  histological  feature  of 
the  vermiform  process  in  the  adult  (Fig.  267).  It  may  invade  and  partly 


FIG.  267. — TRANSVERSE  SECTION  OF  THE  HUMAN  VERMIFORM  PROCESS.     X  20.     (Sobotta.) 

Note  the  absence  of  villi  and  the  abundance  of  nodules.     Clear  spaces  in  the  submucosa  are  fat  cells.     Only 

a  part  of  the  circular  layer  of  the  muscularis  has  been  drawn. 


break  up  the  muscularis  mucosae,  and  extend  into  the  submucosa.  The 
latter,  together  with  the  inner  circular  and  outer  longitudinal  muscle 
layers,  and  the  serosa,  are  similar  to  the  corresponding  layers  of  the  small 
intestine,  already  described. 

During  the  fifth  month  of  embryonic  life,  Stohr  has  found  an  interesting  normal 
form  of  degeneration  in  the  glands  of  the  vermiform  process  (Arch,  f .  mikr.  Anat.,  1898, 
vol.  51,  pp.  1-55).  The  tunica  propria  around  them  appears  to  thicken,  and  the  goblet 
cells  in  the  neck  of  the  degenerating  gland,  after  becoming  flattened,  produce  a  solid 
strand.  The  strand  then  ruptures  and  the  detached  fundus  becomes  cystic.  Subse- 
quently it  shrinks  to  a  small  nodule  surrounded  by  dense  connective  tissue,  and 
ultimately  disappears.  This  degeneration  is  said  to  be  limited  to  the  fifth  and 
sixth  months. 

The  lumen  of  the  normal  vermiform  process  in  the  adult,  when  empty, 
is  thrown  into  folds,  between  which  are  deep  pockets;  but  the  normal  con- 


272 


HISTOLOGY 


dition  is  found  in  scarcely  50%  of  individuals  over  forty  years  of  age 
(Stohr).  Often  the  lumen  is  narrowed  or  even  obliterated.  The  epithe- 
lium with  its  glands  and  the  lymphoid  nodules  then  disappear,  and  are 
replaced  by  an  axial  mass  of  fibrous  tissue.  This  is  surrounded  by  the 
unaltered  submucosa  and  muscularis;  the  serosa  may  show  the  results  of 
inflammatory  conditions. 


CAECUM  AND  COLON. 

The  human  caecum  and  colon  contain  villi  only  in  the  embryo.  These 
villi  disappear  at  about  the  sixth  month.  The  production  of  new  cells 
does  not  keep  pace  with  the  expansion  of  the  epithelial  tube,  and  the  villi 


Glands. 


Fat  cells. 


Solitary  nodule  with  germinal  center. 


FIG.  268. — VERTICAL  SECTION  OF  THE  Mucous  MEMBRANE  OF  THE  DESCENDING  COLON  OF  AN  ADULT 

MAN.     X  80. 

The  fat  has  been  blackened  with  osmic  acid.     Compare  the  length  of  the  glands  with  those  of  the  small 
intestine  (Fig.  260),  from  the  same  individual  and  drawn  under  the  same  magnification. 

therefore  gradually  flatten  and  disappear.  In  the  parts  of  the  embryonic 
intestine  distended  with  secretions  and  desquamated  cells  (constituting 
the  meconium),  the  villi  disappear  earlier  than  in  the  contracted  portions 
(Johnson) . 

After  the  villi  have  gone,  the  mucosa  contains  only  tubular  pits  or 
glands,  lined  with  simple  columnar  epithelium  (Fig.  268).  These  glands 
are  similar  to  those  in  the  small  intestine  but  are  longer — sometimes 
twice  as  long  (0.4-0.6  mm.).  They  contain  more  goblet  cells,  but  cells 


LARGE  INTESTINE  273 

of  Paneth  are  absent.  Striated  cuticular  borders  appear  near  the  out- 
lets of  the  glands,  and  are  well  developed  upon  the  columnar  cells  lining 
the  intestinal  lumen.  Solitary  nodules  are  numerous,  especially  in  the 
caecum.  They  may  extend  through  the  muscularis  mucosae  and  expand 
in  a  flask-shaped  manner  in  the  submucosa  (Fig.  268) ;  in  peripheral  sections 
of  such  a  nodule  the  stalk  by •  which  it  joins  the  tunica  propria  may  not  be 
included,  and  the  area  of  lymphoid  tissue  may  seem  to  be  wholly  in  the 
submucosa.  The  latter  is  a  connective  tissue  layer  like  that  of  the  small 
intestine. 

The  tunica  muscularis  of  the  colon  and  caecum  has  a  characteristic 
arrangement  not  found  in   the  vermiform  process.     The  longitudinal 
smooth  muscle  fibers  of  the  outer  layer  be- 
come gathered  into  three  equidistant  longi- 
tudinal bands  or  tania  (Fig.  269);  between 
them  the  longitudinal  fibers  form  a  thin  layer 
which  may  be  interrupted.     The  taeniae  come 
together  at  the  root  of  the  vermiform  process 
and  are  continuous  with  its  outer  muscle 
layer.     Since  the  longitudinal  muscle  layer 
does  not  elongate  as  rapidly  as  the  parts 
within  it,  the  inner  layer  of  circular  smooth   v 
muscle,  together  with  the  mucosa  and  sub- 
mucosa, become  thrown  into  a  succession  of 
transverse   crescentic   folds    or  plica  semi-  _ 

FIG.  269. — VERMIFORM  PROCESS  (V.  p.), 

lunar es.     The  horns  of  the  crescents  are  op-       uSS?  i^ AH? 


posite  the  taeniae.     Between  the  semilunar        (After  sobotta.) 

h.,  Haustra;  t.,  taema. 

folds  the  wall  of  the  large  intestine  bulges 

outward,  forming  the  haustra  (Lat.,  buckets)  as  shown  in  Fig.  269.  The 
valve  of  the  colon  (valvula  coli)  is  a  pair  of  folds  or  labia,  which  resemble 
the  semilunar  folds;  that  is,  they  include  fibers  of  the  circular  muscle  layer, 
but  the  layer  of  longitudinal  fibers  passes  directly  from  theileum  to  the  colon 
without  entering  the  valves.  The  serosa  of  the  colon  contains  lobules  of 
fat  which  form  pendulous  projectious  known  as  appendices  epiploica. 

RECTUM. 

The  rectum  is  divided  into  two  parts,  an  upper  which  extends  from  the 
third  sacral  vertebra  to  the  pelvic  diaphragm,  and  a  lower  which  continues 
downward  to  the  anus.  The  lining  of  the  first  part  is  thrown  into  several 
folds,  the  plica  transfer  sales  recti  (valves  of  Houston).  These  are  large 
semilunar  folds  which  usually  extend  only  part  way  around  the  rectum, 
but  they  have  been  described  in  some  cases  as  having  a  spiral  arrange- 
ment. The  second  part  of  the  rectum,  the  pars  analis  recti  (anal  canal), 

18 


274 


HISTOLOGY 


presents  on  its  inner  wall  a  number  of  longitudinal  folds,  known  as  rectal 
columns  (columns  of  Glisson  or  Morgagni).     At  their  lower  extremities 


the  columns  unite  with  one  another,  thus  forming  small  transverse  plicae 


Rectal  gland.  


Linea  ano-rectalis. 


Zona  columnaris. 


Linea  sinuosa  analis.  —: 


Zona  intermedia.     < 


Linea  ano-cutanea. 


Circular  layer  of 
smooth  muscle. 


Longitudinal  layer 
of  smooth' muscle. 


Levator  ani. 


Internal  sphincter. 


Intramuscular  gland. 


External  sphincter. 


Sheath  of  a  hair. 
Sebaceous  gland. 


Zona  cutanea. 

FIG.  270. — LONGITUDINAL  SECTION  THROUGH  THE  PARS  ANALIS  RECTI. 
From  a  human  embryo  of  187  mm.  (about  four  months).     (F.  P.  Johnson.) 

or  anal  valves.     The  grooves  between  the  columns  extend  downward  be- 
hind the  valves,  forming  a  series  of  blind  pockets,  the  sinus  rectales. 

The  mucous  membrane  of  the  first  part  of  the  rectum  is  similar  to 
that  of  the  colon,  but  its  glands  are  somewhat  longer  (0.7  mm.).     Soli- 


RECTUM  275 

tary  nodules  are  present.  The  muscularis  mucosae,  submucosa,  and  cir- 
cular layer  of  smooth  muscle  also  resemble  those  of  the  colon,  but  the 
three  taeniae  spread  out  and  unite  so  as  to  form  a  continuous  layer  of 
longitudinal  muscle.  In  the  upper  part  of  the  rectum  this  layer  is  spe- 
cially thickened  dorsally  and  ventrally.  As  the  rectum  loses  its  mesen- 
tery, the  tunica  serosa  is  replaced  by  adventitious  connective  tissue. 

The  pars  analis  recti  is  the  region  of  transition  from  mucous  mem- 
brane to  skin.  This  transition  is  not  gradual  but  takes  place  in  three 
steps,  thus  forming  three  distinct  superimposed  zones.  From  above 
downward  these  are  the  zona  columnaris,  zona  intermedia,  and  zona  cutanea 
(Fig.  2  70) .  The  last,  however,  does  not  belong  to  the  pars  analis,  properly 
speaking,  but  to  the  outside  skin. 

The  zona  columnaris  is  the  region  of  the  rectal  columns,  but  these  are 
not  always  limited  to  this  zone.  They  may  extend  upward  into  the  first 
part  of  the  rectum  for  a  short  distance,  and  they  may  also  be  continuous 
downward  with  the  so-called  anal  skin  folds.  In  the  upper  part  of  the 
zona  columnaris  the  simple  columnar  epithelium  of  the  superior  portion 
of  the  rectum  becomes  two-  or  three-layered.  Its  outer  cells  are  columnar, 
with  finely  granular  protoplasm.  The  transition  takes  place  gradually 
at  the  linea  ano-rectalis.  In  the  upper  part  of  the  zone  there  are  usually 
a  few  intestinal  glands  containing  numerous  goblet  cells,  and  a  few  goblet 
cells  are  found  also  in  the  surface  epithelium.  In  the  lower  part  of  the 
zona  columnaris,  arising  from  the  rectal  sinuses,  there  are  a  few  branched 
tubular  gland-like  structures,  the  infra-muscular  glands  (Fig.  270). 
There  are  seldom  more  than  six  or  eight  in  any  one  rectum.  The  main 
ducts  of  these  glands  extend  outward,  and  usually  downward,  and  pene- 
trate the  internal  circular  muscle  (internal  sphincter).  Here  a  flask- 
shaped  swelling  is  usually  met  with.  Extending  beyond  this  ampulla  there 
are  several  tubular  branches  which  continue  through  the  internal  sphincter 
and  end  blindly  in  the  intra-muscular  connective  tissue.  Occasionally  a 
tubule  is  seen  piercing  the  longitudinal  muscle  layer.  Around  the  termi- 
nations of  the  tubules,  which  are  sometimes  swollen,  there  is  a  small  amount 
of  lymphoid  tissue.  The  epithelium  lining  the  main  ducts  of  these  glands 
consists  of  several  layers  of  polygonal  cells,  but  the  ampullae  and  branches 
are  lined  with  one  or  two  layers  of  cuboidal  cells.  Secretory  cells  are 
present  in  the  embryo  and  at  birth,  but  are  apparently  wanting  in  the 
adult. 

The  transition  between  the  zona  columnaris  and  zona  intermedia  is 
marked  by  a  rather  abrupt  change  in  the  epithelium,  which  becomes  many 
layered  and  squamous.  This  transition  takes  place  at  the  level  of  the 
anal  valves,  but  between  the  valves  it  extends  upward  on  the  rectal  col- 
umns. Thus  it  follows  a  zig-zag  line,  the  linea  sinuosa  analis  (ano-cutane- 
ous  line  of  Hermann).  Within  the  zona  intermedia  the  epithelium,  com- 


276  HISTOLOGY 

posed  of  several  layers  of  polygonal  cells,  is  thicker  than  the  epidermis. 
Dermal  papillae  are  present,  but  hairs  and  sweat  glands  are  absent. 
In  the  lower  part  of  this  zone  there  are  a  few  isolated  sebaceous  glands 
without  hairs,  and  the  epithelium  is  slightly  cornined.  Thus  it  gradually 
goes  over  into  skin,  forming  a  true  linea  ano-cutanea,  but  this  line  is  not 
well  marked.  It  has  been  denned  as  the  place  where  the  first  sheaths  of 
the  hairs  appear. 

The  skin  immediately  surrounding  the  anus  forms  the  zona  cutanea. 
Sweat  glands  are  absent  from  the  region  bordering  on  the  anus,  but  at  a 
distance  of  1.0-1.5  cm.  there  is  an  elliptical  zone,  1.25-1.5  cm.  wide,  con- 
taining simple  tubular  coiled  glands,  the  circum-anal  glands  of  Gay. 
These  are  very  similar  to  sweat  glands  but  are  considerably  larger. 

The  outer  layers  of  the  pars  analis  recti  include  a  very  vascular  tela 
submucosa,  which  contains  numerous  nerves  and  lamellar  corpuscles. 
The  muscularis  mucosae  terminates  in  slender  longitudinal  bundles  which 
extend  for  varying  distances  into  the  rectal  columns  (forming  the  M. 
dilatator  ani  internus  of  Riidinger).  The  circular.layer  of  the  tunica  mus- 
cularis becomes  thickened  at  its  termination,  forming  the  M.  sphincter 
ani  internus;  it  extends  a  little  below  the  the  linea  sinuosa  analis.  Beyond 
the  internal  sphincter,  which  is  composed  of  smooth  muscle,  striated  muscle 
fibers  surround  the  anus  forming  the  M.  sphincter  ani  externus.  The 
outer  longitudinal-  layer  of  the  tunica  muscularis  ends  in  relation  with 
connective  tissue  strands  which  diverge  as  they  pass  downward  through 
the  external  sphincter,  to  terminate  in  the  subepithelial  tissue  of  the  zona 
cutanea. 

LIVER. 
DEVELOPMENT  AND  GENERAL  STRUCTURE. 

The  liver  first  appears  in  human  embryos  of  about  2.5  mm.  as  a  diver  ticu- 
lum  of  the  ventral  wall  of  the  fore-gut,  near  its  junction  with  the  yolk-sac. 
If  the  embryo  is  placed  in  an  upright  position  (Fig.  271,  A)  the  liver  is 
seen  to  be  below  the  heart,  and  between  the  vitelline  veins  as  they  pass  from 
the  yolk-sac  to  their  cardiac  termination.  The  diver  tic  ulum  projects  into 
a  mass  of  mesoderm,  to  which  His  gave  the  old  anatomical  term  for  dia- 
phragm, namely  septum  transversum.  The  diaphragm  develops  in  the 
anterior  or  upper  part  of  this  septum;  the  lower  or  posterior  part  constitutes 
the  ventral  mesentery,  which  extends  from  the  fore-gut  to  the  ventral 
body  wall.  The  hepatic  diverticulum  is  in  the  mesenteric  part  of  the  sep- 
tum, although  it  is  always  connected  with  the  overlying  diaphragmatic 
shelf. 

Very  early  the  liver  becomes  divided  into  two  parts,  (i)  the  somewhat 
rounded  diverticulum  proper,  lined  with  columnar  cells  with  pale  proto- 


LIVER 


277 


plasm,  and  (2)  a  mass  of  anastomosing  cords  or  trabeculae,  composed  of 
deeply  staining  cells  with  round  nuclei  and  abundant  granular  protoplasm. 
These  two  parts  are  so  unlike  in  appearance  that  they  have  been  thought 
to  proceed  from  different  germ  layers,  the  trabeculae  being  described  as 
formed  from  mesenchyma  in  the  septum  transversum.  This  opinion  is 
erroneous;  the  entire  structure  is  entodermal,  and  the  trabeculae  grow  out 
from  the  diverticulum.  They  encounter  the  vitelline  veins,  which  ramify 
around  them,  producing  the  lacunar  vessels  or  sinusoids  already  described 
(Fig.  160,  p.  167). 

In  an  embryo  of  io-i2mm.  (Fig.  271,  B),  the  hepatic  diverticulum 
has  elongated  and  is  connected  with  the  mass  of  anastomosing  trabeculae 
at  several  points.  It  shows  also  some  detached  ducts  and  round  knob-like 


p.c 


FIG.  271. — DIAGRAMS  OF  THE  DEVELOPMENT  OF  THE  LIVER. 

A,  From  a  4.o-mm.  human  embryo.  B,  From  a  12-mm.  pig.  C,  The  ducts  in  the  human  adult,  c.  d., 
Cystic  duct;  c.  p.,  perit9neal  cavity;  d.,  duodenum;  d.  c.,  ductus  choledochus;  dia.,  diaphragm;  div., 
distal  end  of  the  diverticulum;  f.  1.,  falciform  ligament;  g.  b.,  gall  bladder;  g.  o.,  greater  omentum; 
h.  d.,  hepatic  duct;  ht.,  heart;  int.,  intestine;  li.,  liver;  1.  o.,  lesser  omentum;  m.,  mediastinum;  oe., 
oesophagus;  p.  c.,  pericardial  cavity;  p.  d.,  pancreatic  duct;  ph.,  pharynx;  p.  y.,  portal  vein;  s.  t.,  septum 
transversum;  st.,  stomach;  tr.,  trabecula ;  v.  c.  i.,  vena  cava  inferior;  v.  v.,  vitelline  vein;  y.  s.,  yolk-sac. 

swellings.  The  vitelline  veins  have  given  rise  to  the  portal  vein,  which 
enters  the  liver  from  below  and  breaks  up  into  sinusoids  among  the 
trabeculae.  These  reunite,  and  leave  the  liver  above  as  the  hepatic  vein, 
which  was  originally  a  part  of  the  vitelline  veins.  In  the  lo-mm.  embryo 
the  circulation  of  the  liver  is  wholly  venous.  The  trabeculae  consist  of 
cells  which  are  doubtless  very  active,  taking  up  and  transforming  material 
received  from  the  blood,  but  it  may  be  questioned  whether  bile  is  secreted 
at  this  stage,  since  no  complete  system  of  ducts  has  been  demonstrated. 

In  later  stages  the  mass  of  anastomosing  trabeculae  is  drained  by  a 
system  of  ducts  lined  with  clear  cuboidal  or  columnar  epithelium.  These 
all  empty  into  a  single  hepatic  duct,  which  represents  one  of  the  original 
connections  between  the  trabeculae  and  the  diverticulum.  (In  the  otter 
there  are  said  to  be  as  many  as  seven  persistent  ducts.)  The  hepatic 
duct  (Fig.  271,  C)  is  joined  by  the  cystic  duct  which  comes  from  the  taper- 
ing pyriform  gall  bladder  (vesica  fellea) .  The  latter  is  perhaps  to  be  re- 


278  HISTOLOGY 

garded  as  a  special  subdivision  of  the  original  diverticulum,  rather  than  as 
its  expanded  terminal  portion.  In  certain  mammals,  as  in  the  horse  and 
elephant,  the  gall  bladder  is  lacking.  After  the  hepatic  duct  has  joined 
the  cystic  duct,  the  common  bile  duct  (ductus  choledochus)  thus  formed 
proceeds  to  the  duodenum  into  which  it  opens,  together  with  the  pancreatic 
duct,  at  the  duodenal  papilla.  The  common  bile  duct  is  an  elongated 
portion  of  the  original  hepatic  diverticulum. 

Ligaments  of  the  Liver.  At  the  time  of  its  earliest  formation  the  liver 
bulges  laterally  from  the  ventral  mesentery,  on  both  sides,  thus  forming 
right  and  left  lobes.  The  lobes  are  covered  with  the  peritoneal  epithelium. 

The  mesenchyma  beneath  this  epithelium  pro- 
duces  loose  connective  tissue  externally,  and  a 
dense  fibrous  tissue,  immediately  surrounding 
the  trabeculae,  internally;  this  latter  becomes 
the  capsula  fibrosa  (or  capsule  of  Glisson). 
The  part  of  the  ventral  mesentery  extending 
from  the  intestine  to  the  liver  is  known  as  the 
lesser  omentum,  and  the  part  between  the  liver 
and  the  ventral  body  wall  is  the  falciform  liga- 
FIG.  272.—  THE  LEFT  SIDE  OF  AN  went.  These  lie  in  the  median  plane  (Fig.  272). 
'  Beneath  the  liver,  the  peritoneal  cavity  comes 

d'        "  to  extend  across  the  median  line  so  that  the 

gal1  bladder  is  covered  with  peritoneum,  except 
along  its  attachment  to  the  under  side  of  the 


liver.     On  the  upper  surface  of  the  liver,  the 

original  broad  connection  with  the  septum  transversum  becomes  rela- 
tively narrow  dorso-ventrally,  and  forms  a  pair  of  lateral  ligaments  which 
pass  from  the  upper  surface  of  the  liver  to  the  diaphragm.  They  extend 
across  the  liver  at  right  angles  with  the  falciform  ligament  and  lesser 
omentum.  The  left  lateral  ligament  retains  these  simple  relations  and  is 
known  as  the  left  triangular  ligament.  The  right  lateral  ligament,  except 
at  .its  tip  (the  right  triangular  ligament),  extends  down  over  the  posterior 
surface  of  the  liver  as  an  extensive  area  of  fusion  with  the  diaphragm;  this 
iskAthe  coronary  ligament  (Fig.  275).  The  significance  of  this  asym- 
metrical condition  will  be  explained  with  the  veins  of  the  liver. 

Development  of  the  veins  of  the  liver.  The  hepatic  trabeculae  are  always 
in  close  relation  with  the  veins  which  are  conveying  nutriment  to  the 
heart.  These  are  (i)  the  vitelline  veins  conveying  nutriment  from  the 
yolk-sac,  (2)  the  umbilical  veins  conveying  nutriment  from  the  placenta, 
and  (3)  the  portal  vein  conveying  absorbed  food  from  the  intestine.  The 
liver  also  has  important  relations  with  the  vena  cava  inferior. 

The  portal  vein,  which  is  the  principal  afferent  vessel  of  the  adult  liver,  is  derived 
from  the  vitelline  veins.  The  latter,  as  they  pass  from  the  yolk-sac  into  the  abdominal 


LIVER  279 

cavity,  fuse  with  one  another  so  as  to  form  a  single  trunk  (Fig.  271,  B,  v.v.).  On 
reaching  the  duodenum,  the  trunk  separates  into  its  components,  and  they  pass  into  the 
liver  as  the  right  and  left  vitelline  veins  (Fig.  273,  A).  Before  entering  the  liver  they 
anastomose  with  one  another  dorsal  to  the  duodenum,  as  shown  in  the  figure.  Thus, 
with  the  connections  between  the  right  and  left  veins  within  the  liver,  two  complete 
venous  rings  are  formed  around  the  intestine.  Branches  extend  out  from  these  rings, 
notably  the  superior  mesenteric  vein  which  receives  blood  from  the  primary  loop  of 
intestine,  and  the  splenic  vein  which  not  only  drains  the  spleen  but  receives  the  inferior 
mesenteric  vein  together  with  pancreatic  and  gastric  branches.  The  superior  mesenteric 
vein  (Fig.  273,  s.m.v.)  is  joined  by  the  splenic  (s.)  to  form  the  portal  vein  (p.v.),  and  the 
portal  vein  is  a  persistent  portion  of  the  peri-intestinal  rings  formed  by  the  vitelline 
veins.  Other  parts  of  the  rings  atrophy,  and  as  the  yolk-sac  degenerates  and  becomes 
detached,  the  main  vitelline  trunk  disappears.  The 
portal  system  of  veins  is  therefore  a  derivative  of 
the  vitelline  system;  its  blood  flows  through  the  liver 
in  the  vitelline  sinusoids. 

The  formation  of  the  rings  as  above  described 
takes  place  with  great  constancy,  and  apparently 
the  only  variations  observed  in  their  atrophy  are  the 
.two  cases  described  by  Begg  (Amer.  Journ.  Anat., 
1912,  vol.  13,  PP.  105-110). 

The  umbilical  veins  are  at  first  a  pair  of  vessels, 
but  they  early  unite  in  the  umbilical  cord.  The  p 

single  vein  thus  formed  brings  the  embryonic  blood  The  formation  9f  the  portal  vein, 
back  to  the  body  after  its  excursion  to  the  placenta. 
On  reaching  the  body,  the  vein  divides  into  right 
and  left  vessels,  which  are  contained  in  the  ventral 
body  wall,  and  at  first  pass  directly  to  the  heart;  later  they  anastomose  with  the 
vitelline  sinusoids  in  the  liver,  and  the  right  umbilical  vein  then  atrophies,  leaving 
the  left  vein  to  convey  the  blood  to  the  liver.  In  Fig.  274,  the  left  vein  is  larger 
than  the  right,  and  is  seen  connecting  with  the  hepatic  sinusoids.  Gradually  it 
shifts  from  the  left  side  to  the  median  line.  It  then  passes  from  the  umbilical 
cord  to  the  under  surface  of  the  liver  along  the  free  edge  of  the  falciform  ligament, 
where,  after  the  umbilical  cord  has  been  severed,  it  degenerates  to  form  the  round 
ligament  of  the  liver  (Fig.  275).  This  extends  to  the  porta  or  entrance  to  the  liver, 
where  the  portal  vein  goes  in  and  the  hepatic  duct  comes  out.  Beyond  this  point 
the  umbilical  vein  may  be  followed  as  the  ductus  venosus  in  the  embryo,  or  the 
ligament  of  the  ductus  venosus  in  the  adult,  to  the  vena  cava  inferior.  The  ductus 
venosus  may  be  defined  as  the  channel  made  by  the  umbilical  vein  in  passing  to  the 
vena  cava  inferior  across  the  under  surface  of  the  liver.  It  is  sometimes  completely 
enfolded  by  the  hepatic  trabeculae,  and  it  communicates  with  the  hepatic  sinusoids.  It 
follows  the  line  of  attachment  of  the  lesser  omentum,  and  empties  into  the  vena  cava 
inferior. 

The  vena  cava  inferior  apparently  does  not  send  much  blood  into  the  liver  but  passes 
along  its  dorsal  surface.  An  essential  part  of  this  great  vein  is  formed  from  the  hepatic 
sinusoids.  Before  the  vena  cava  inferior  has  developed,  the  blood  in  the  dorsal  body 
wall  flows  to  the  heart  through  the  posterior  cardinal  veins,  one  on  either  side  of  the 
aorta.  Each  posterior  cardinal  vein  shows  a  ventral  subdivision,  the  right  and  left 
subcardinal  veins  respectively,  which  are  seen  in  section  in  Fig.  274.  As  shown  in  the 
figure,  the  stomach  prevents  the  liver  from  approaching  the  dorsal  body  wall  (at  the 
root  of  the  mesentery)  on  the  left,  but  on  the  right  there  is  no  such  obstruction,  and  the 


280 


HISTOLOGY 


liver  approaches  and  fuses  with  the  body  wall  immediately  in  front  of  the  right  subcar- 
dinalvein.  This  fusion  constitutes  the  coronary  ligament  (cf.  Fig.  275);  and  across  it, 
the  subcardinal  vein  anastomoses  with  the  hepatic  sinusoids.  By  a  rapid  enlargement 
of  this  anastomosis,  the  trunk  of  the  vena  cava  inferior  is  formed.  It  drains  the 
posterior  cardinal  system  of  veins,  and  the  outlet  of  the  vitelline  veins  into  the  heart  be- 
comes the  terminal  portion  of  the  inferior  vena  cava;  the  main  vessel  from  the  liver,  the 
hepatic  vein,  is  thereafter  described  as  a  branch  of  the  vena  cava  inferior.  The  devel- 
opment of  the  posterior  part  of  the  vena  cava  inferior  is  described  in  connection  with 
the  Wolffian  body  (p.  309);  for  a  fuller  account,  see  the  Amer.  Journ.  Anat.,  1902,  vol. 
i,  pp.  229-244.  Occasionally  the  trunk  of  the  vena  cava  is  entirely  surrounded  by  a 
band  of  hepatic  tissue,  as  iir  Fig.  275. 


rs-c.v.  .../  ; 


l.s-c.v. 


r.t.l. 


A -4 -1-0. 


f.l.   v.um. 

FIG.  274. — CROSS  SECTION  OF  A  MAMMALIAN 
EMBRYO,  TO  SHOW  THE  ADHESION,  x,  BE- 
TWEEN THE  RIGHT  LOBE  OF  THE  LIVER  AND 
THE  DORSAL  ABDOMINAL  WALL. 

ao.,  Aorta;  f.  c.,  fibrous  capsule  and  serosa;  f.  1., 
falciform  ligament;  g.  o.,  greater  omentum; 
1.  o.,  lesser  omentum;  1.  s-c.  v.,  left  subcar- 
dinal vein;  o.  b.,  omental  bursa;  r.  s-c.  v., 
right  subcardinal  vein;  St.,  stomach;  v.  um., 
left  umbilical  vein. 


FIG.  275. — DORSAL  SURFACE  OF  THE  ADULT 
LIVER. 

c.  1.,  Coronary  ligament;  f.  1.,  falciform  liga- 
ment; g.  b.,  gall  bladder;  1.  o.,  lesser 
omentum;  1.  1. 1.,  left  triangular  ligament; 
o.  b.,  caudate  lobe  bounding  the  omental 
bursa  ventrally;  p.  v.,  portal  vein;  r.  1., 
round  ligament;  r.  t.  1.,  right  triangular 
ligament;  v.  c.  i.,  vena  cava  inferior. 


Lobes  o]  the  liver.  The  structures  already  described  form  the  bound- 
aries of  the  lobes  of  the  liver,  which  in  man  are  few  and  not  sharply  marked 
out.  Right  and  left  lobes  have  already  been  mentioned  as  the  lateral 
halves  of  the  liver;  they  are  not  separated  from  one  another  by  any  internal 
septum  or  indentation  of  the  surface.  The  left  lobe  is  relatively  small,  and 
has  a  thin  margin.  It  terminates  in  the  appendix  fibros a  at  the  extremity 
of  the  left  triangular  ligament.  This  appendix  represents  a  portion  of  the 
liver  from  which  the  hepatic  cells  have  degenerated  and  disappeared,  leav- 
ing chiefly  the  anastomosing  ducts.  It  indicates  that  in  earlier  stages  the 
left  lobe  was  more  extensively  developed.  Similar  tissue  containing 
aberrant  ducts  (vasa  aberrantia)  may  be  found  around  the  vena  cava  and 
in  some  other  parts  of  the  liver.  The  quadrate  lobe  is  marked  cut  by  the 
port  a,  the  round  ligament,  and  the  fossa  containing  the  gall  bladder.  The 
caudate  lobe  is  bounded  by  coronary  ligament,  lesser  omentum  and  porta. 
The  caudate  process  of  this  lobe  extends  to  the  right  lobe  over  thejoramen 
epiploicum  (of  Winslow)  between  the  vena  cava  and  the  porta. 

The  hepatic  artery.  The  liver  in  an  embryo  of  10  mm.  has  no  arteries, 
but  at  that  stage  the  hepatic  artery  can  be  followed  to  the  porta.  Later  it 


LIVER 


28l 


extends  through  the  connective  tissue  around  the  gall  bladder,  so  that  the 
cystic  branch  of  the  adult  appears  to  be  the  main  vessel  in  the  young  em- 
bryo. Still  later,  as  the  connective  tissue  which  surrounds  the  structures 
at  the  porta  gradually  extends  into  the  liver  around  the  branches  of  the 
hepatic  duct  and  portal  vein,  the  hepatic  artery  sends  branches  in  with  it, 
and  they  form  capillaries  which  empty  into  the  adjacent  portal  sinusoids. 
Branches  of  the  artery  ramify  also  in  the  connective  tissue  capsule  around 
the  entire  liver.  The  quantity  of  blood  supplied  to  the  liver  by  the  artery 
always  remains  much  smaller  than  that  brought  in  by  the  portal  vein,  and 
it  is  distributed  to  the  connective  tissue.  There  are  no  vessels  between 
the  hepatic  cells  other  than  the  "capilliform  sinusoids"  derived  directly 
from  the  embryonic  lacunae  of  the  vitelline  veins. 

MICROSCOPIC   STRUCTURE. 

Lobules.  A  section  of  the  embryonic  liver,  or  of  the  liver  at  birth,  shows 
great  areas  of  anastomosing  trabeculae,  with  intervening  sinusoids  and  oc- 
casionally a  larger  vein.  In  the  adult  pig  the  hepatic  tissue  is  arranged  in 
lobulrs  bounded  by  connective  tissue  (Fig.  276).  These  subdivisions  were 


FIG.  276. — LIVER  OF  A  PIG.     (Radasch.) 

The  lobules  have  artificially  shrunken  from  the  interlobular  tissue,  a;  b,  bile  duct;  c,  hepatic  artery; 
d,   interlobular  vein  (a  branch  of  the  portal);  e,  trabeculae;  f,  central  vein. 

first  recognized  in  the  liver  of  the  pig  (Wepfer,  1664),  and  in  1666  Malpighi 
made  the  general  statement  that  the  entire  liver  is  composed  of  a  multi- 
plicity of  lobules.  In  the  dog  Mall  finds  that  the  lobules  are  short  cylinders 


282 


HISTOLOGY 


averaging  0.7  mm.  high  and  0.7  mm.  in  diameter,  and  that  the  entire  liver 
(of  175  c.c.)  contains  480,000  of  them  (Amer.  Journ.  Anat.,  1906,  vol.  5, 
pp.  227-308).  There  has  been  prolonged  discussion  as  to  whether  the 
lobules  should  be  regarded  as  centering  about  the  terminal  branches  of  the 
portal  vein  or  around  those  of  the  hepatic  vein,  for,  although  it  was  fre- 
quently stated  that  they  were  arranged  like  a  bunch  of  grapes,  there  was 
no  unanimity  as  to  what  formed  the  stem.  If  the  human  liver  is  examined 
(Fig.  277)  it  is  seen  that  the  lobules  are  not  definitely  marked  out  as  in  the 
pig,  but  the  liver  retains  to  a  greater  extent  its  embryonic  appearance. 
Scattered  about  through  the  section,  bat  at  quite  uniform  distances  from 
one  another,  there  are  islands  of  connective  tissue  containing  branches 
of  the  portal  vein,  hepatic  artery,  and  bile  duct.  The  strands  of  connective 


Branch  of  portal  vein. 

',  '  «   .•/,,*-  .  Large  interlobular  bile  duct. 


Interlobular  connective 
tissue. 


Central  veins. 


Central  vein. 


\*k.'  'i-ftty"  >,  •  "-  /*  t  '•••»'  ^'&tM^M§5iaV5*(jy^ 

, »*&;*?• >*„ *•£ •-*/•* ?~ v ' .,'  \  •>*%•-'•' *  l  £* 

»•  **  Si 

FIG.  277. — FROM  A  TANGENTIAL  SECTION  OF  THE  HUMAN  LIVER.     X  40. 

The  three  central.;veins  in  cross  section  mark  the  centers  of  three  lobules,  which  are  not  sharply  separated, 
at  the  periphery,  from  their  neighbors.  Below  and  at  the  right  the  lobules  are  cut  obliquely  and  their 
boundaries  are  not'seen. 

tissue  which  conduct  the  portal  branches  were  named  portal  canals  by 
Kiernan  (Trans.  Roy.  Soc.  London,  1833,  pp.  711-770).  If  the  connective 
tissue  should  spread  from  one  canal  to  another,  connecting  those  nearest 
together,  it  would  mark  out  lobules  like  those  in  the  pig's  liver,  and  this 
sometimes  takes  place  pathologically  in  man.  Normally  the  portal  canals 
stand  as  isolated  "boundary  stones." 

Within  each  lobule  thus  marked  out  there  is  a  central  vein  or  enlarged 
sinusoid,  toward  which  the  capilliform  sinusoids  between  the  hepatic 
trabeculae  converge.  Occasionally  there  are  two  veins,  side  by  side. 
These  central  veins  empty  at  right  angles  into  sublobttlar  veins  (Fig.  278), 
which  come  together  to  form  the  main  branches  of  the  hepatic  vein.  All 
these  veins,  in  contrast  with  the  portal  branches,  have  very  little  connective 
tissue  around  them,  and  they  are  not  associated  with  bile  ducts  or  arteries; 


LIVER 


283 


thus  the  hepatic  veins  are  readily  distinguished  from  the  portal  veins. 
The  flow  of  the  blood  (Fig.  279)  is  from  the  portal  veins  (in  the  portal 
canals)  through  the  capilliform  sinusoids  to  the  central  veins,  thence 


Hepatic  lobules. 


Interlobular  connective 
tissue. 


Central  (intralobular) 


£ Sublobular  vein. 


FIG.  278. — FROM  A  VERTICAL  SECTION  OF  A  CAT'S  LIVER,  INJECTED  THROUGH  THE^VENA  CAVA  INFERIOR. 
The  central  veins  and  the  sublobular  vein  into  which  they  empty  are  cut  longitudinally.      X  IS- 


Two  bile  ducts  in 

cross  section.      


Capilliform  ^ 
sinusoids.    *^— - 


Central  vein. 


Interlobular  vein 
(branch  of  portal). 


PIG.  279. — FROM  A  SECTION  OF  THE  HUMAN  ADULT  LIVER  INJECTED 
THROUGH  THE  PORTAL  VEIN. 

through  the  sublobular  veins  into  the  hepatic  vein,  which  empties  into  the 
vena  cava  inferior.  The  arteries  empty  through  capillaries  into  the 
capilliform  sinusoids  adjacent  to  the  portal  canals,  and  there  is  some 


284  HISTOLOGY 

evidence  that  the  hepatic  cells  at  the  periphery  of  the  lobule  are  better 
nourished  than  those  in  its  interior. 

The  recognition  of  the  lobules  above  described,  as  the  essential  basis 
of  hepatic  structure,  would  have  been  unquestioned  except  that,  as  Kier- 
nan  stated,  "the  essential  part  of  the  gland  is  undoubtedly  its  duct;  vessels 
it  possesses  in  common  with  every  other  organ;  and  it  may  be  thought  that 
in  the  above  description  too  much  importance  is  attached  to  the  hepatic 
veins."  If  the  liver  were  divided  into  lobules  comparable  with  those  of 
other  glands,  the  portal  canals  with  their  ducts  and  adjacent  afferent  ves- 
sels would  be  the  axial  structures,  and  the  efferent  central  veins  would  be 
peripheral.  By  connecting  the  five*  central  veins  around  the  portal  canal 
in  Fig.  277  (two  of  the  central  veins  are  not  labelled  and  the  one  at  the 
lower  edge  of  the  figure  is  indistinct) ,  such  a  structural  unit  or  secretory  unit 
would  be  marked  out.  It  has  been  proposed  to  call  it  a  portal  lobule  (from 
its  axial  structure),  in  contrast  with  the  hepatic  lobules,  which  surround  the 
branches  -of  the  hepatic  vein.  In  the  seal  it  is  said  that  the  portal  lobules, 
or  units,  are  bounded  by  connective  tissue,  but  this  must  be  regarded  as 
very  exceptional.  However,  in  attempting  to  picture  the  complex  rela- 
tions of  the  lobules  in  the  liver,  the  morphologist  must  regard  the  portal 
canals  as  axial,  even  though  the  term  lobule  is  used  for  areas  surrounding 
the  central  veins.  The  bile  flows  from  parts  of  several  hepatic  lobules 
into  a  single  portal  canal. 

Parenchyma.  The  parenchyma  or  essential  tissue  of  the  liver  is  found 
in  the  anastomosing  trabeculae  of  the  lobules.  The  general  arrangement 
of  the  cells  in  these  trabeculas  is  shown  in  Fig.  280,  in  which,  however, 
the  slender  lumens  are  rendered  conspicuous  by  special  treatment.  These 
lumens,  or  bile  capillaries,  are  ordinarily  inconspicuous,  and  the  trabeculas 
appear  on  superficial  examination  as  solid  cords  of  cuboidal  cells,  with 
abundant  granular  protoplasm  and  large  round  central  nuclei.  Often 
the  hepatic  cells  contain  two  nuclei,  and  large  cells  with  several  nuclei, 
produced  by  amitosis,  have  been  reported.  The  general  characteristics 
of  hepatic  cells  are  shown  in  Fig.  281.  They  are  arranged  chiefly  in  double 
rows  which  in  certain  positions  appear  single. 

The  hepatic  cells  have  very  delicate  cell  membranes,  which  are  some- 
times said  to  be  absent.  Their  protoplasm  often  contains  brown  pigment, 
especially  toward  the  central  vein.  Near  the  periphery  of  the  lobule  the 
cells  may  contain  fat  vacuoles  of  varying  size,  found  normally  in  well- 
nourished  individuals.  Pathologically  the  vacuoles  may  be  large  and 
widely  distributed.  Glycogen  (p.  78)  occurs  in  granules  and  larger 
masses,  especially  after  abundant  meals.  In  the  fasting  condition,  the 
cells  are  relatively  small,  dark,  and  obscurely  outlined,  but  during  diges- 
tion they  become  larger  with  a  clearer  central  part  and  a  peripheral  zone 
of  coarse  granules.  In  man  both  conditions  may  be  found  in  one  liver. 


LIVER 


285 


The  bile,  secreted  by  the  hepatic  cells,  probably  through  granule  for- 
mation, frequently  contains  granules  and  fat  droplets  such  as  are  found 
within  the  cells.  It  is  eliminated  through  the  bile  capillaries. 

The  bile  capillaries  are  minute  tubes  with  continuous  cuticular  walls, 
presumably  formed  by  the  local  modification  of  the  cell  membranes  of 
two  adjacent  hepatic  cells.  The  completed  capillary,  however,  shows  no 


True  meshes. 


Lateral  branches  of  bile  capillaries. 


Nucleus  of 

an  hepatic 

cell. 


Nuclei  of 

hepatic 

cells. 


Sinusoids.  Portion  of  a  central  vein. 

FIG.  280.— FROM  A  CROSS  SECTION  OF  A  HUMAN  HEPATIC  LOBULE.     X  300. 

Golgi  preparation.     The  boundaries  of  the  hepatic  cells  could  not  be  seen.     The  black  dots  are  precipi- 
tates of  the  silver. 

indication  of  being  formed  of  lateral  halves  which  have  fused.  Cross 
sections  of  the  large  bile  capillaries  in  the  liver  of  Necturus  are  shown  in 
Fig.  281,  and  their  arrangement  in  the  human  liver  is  indicated  in  Fig.  280. 
They  extend  through  the  axis  of  the  two-rowed  trabeculae  of  cells,  giving 
off  short  intercellular  branches  at  right  angles.  Thus  the  bile  capillaries 
shown  in  Fig.  281  between  the  two  sinusoids,  may  be  separate  axial 


286 


HISTOLOGY 


capillaries,  or  they  may  be  intercellular  branches  of  an  axial  capillary 
which  is  in  the  plane  of  the  printed  page.  In  some  places  the  bile  capil- 
laries completely  encircle  an  hepatic  cell,  forming  "  true  meshes "  (Fig.  280). 
They  may  form  larger  meshes  due  to  the  anastomosis  of  trabeculae.  Occa- 
sionally a  bile  capillary  is  in  relation  with  three  surrounding  hepatic  cells, 
or  even  more,  thus  resembling  the  lumen  of  an  ordinary  gland-tubule. 

In  addition  to  intercellular  capillaries  there  are  said  to  be  intracellular 
branches,  several  of  which  may  penetrate  the  protoplasm  of  a  single  cell 
and  end  in  knobs,  as  shown  by  the  Golgi  method.  Since  neighboring 
capillaries  may  be  free  from  these  branches,  they  are  regarded  as  tempo- 


a  - 


FIG.  281. — SECTION  OF  THE  LIVER  OF  A  SALAMANDER  (Necturus).     X  380. 
a,  Endothelial  cell;  b,  endothelial  reticulum;  c,  blood  vessel;  d,  bile  capillary;  e,  red  corpuscle;  f,  hepatic  cell. 

rary  phases  of  functional  activity,  accompanying  the  discharge  of  secretion. 
They  have  been  reported  as  forming  baskets  within  the  protoplasm, 
similar  to  those  found  in  parietal  cells  of  the  stomach. 

The  bile  capillaries  and  their  branches  are  generally  separated  from 
the  lining  of  the  blood  vessels  by  an  appreciable  portion  of  the  hepatic  cells 
(cf.  Figs.  280  and  281).  Pathologically  they  may  extend  nearer  the  vessels 
and  may  rupture,  so  that  the  bile  escapes  into  the  perivascular  tissue  and 
is  distributed  over  the  body,  causing  jaundice. 

Endothelium  and  Perivascular  Tissue.  The  endothelium  of  the  capil- 
lif  orm  sinusoids  which  border  upon  the  hepatic  trabeculae  is  specially  modi- 
fied; it  is  well  shown  in  the  coarse-grained  liver  of  Necturus  (Fig.  281), 
but  the  same  form  occurs  in  the  human  liver.  The  endothelial  cells,  which 
are  phagocytic,  produce  a  network  of  reticular  fibers  toward  the  hepatic 
cells  (Fig.  282).  The  reticulum  contains  no  elastic  elements,  and  the 
only  cell  bodies  associated  with  it  are  those  of  the  endothelium.  In  the 
reticular  meshworkin  the  embryo,  erythroblasts  multiply  in  great  numbers, 


LIVER 


287 


and  to  some  extent  leucocytes  are  formed,  but  in  the  adult  the  recticulum 
is  free  from  cells.  The  endothelial  cells,  moreover,  do  not  fit  closely 
together,  and  are  known  as  the  stellate  cells  of  Kup/er.  It  is  probable 
that,  whereas  the  blood  flows  through  the  capilliform  sinusoids  toward  the 
central  vein,  there  is  a  current  of  tissue  fluid  in  the  reticulum  taking  the 
reverse  direction  and  passing  toward  the  portal  canal.  This  fluid  is  the 
source  of  the  great  quantity  of  lymph  which  flows  from  the  liver. 

According  to  Schafer  (Quain's  Anatomy,  1912,  vol.  2)  the  blood  flowing 
through  the  sinusoids  comes  into  direct  contact  with  the  liver  cells.  He 
states  that  blood  corpuscles  Hepatic  trabecul£E.  Blood  corpuscies. 
may  occasionally  be  found 
normally  within  the  hepatic 
cells,  into  which  they  are 
readily  forced  by  injections 
at  low  pressure;  and  he  de- 
scribes canaliculi  within  the 
protoplasm  of  the  hepatic 
cells,  which  communicate 
with  the  sinusoidal  blood 
vessels.  These  canaliculi 
are  presumably  secretory 
channels  or  canals  of  the 
trophospongium,  which  have 
been  artificially  invaded  by 
the  injection.  At  the  same  time,  the  reticulum  has  been  compressed  and 
its  significance  obscured. 

Portal  canals.  The  portal  canals  are  strands  of  connective  tissue 
extending  into  the  liver  from  the  transverse  fissure  or  porta  (which  is 
essentially  a  hilus).  They  constitute  the  inter lobular  tissue  of  the  liver, 
and  the  ducts,  arteries,  and  veins  which  they  contain  are  often  called  inter- 
lob  ular.  In  addition  to  the  structures  already  considered,  the  portal 
canals  contain  lymphatics  and  nerves;  these  and  certain  features  of  the 
ducts  require  further  consideration. 

The  lymphatic  vessels  are  abundant,  forming  plexuses  around  the  ducts 
and  blood  vessels,  and  receiving  fluid  from  the  perivascular  reticulum 
within  the  lobules;  but  no  lymphatic  vessels  enter  the  lobules.  They 
pass  out  of  the  liver  at  the  porta,  where  lymph  glands  are  found.  Certain 
of  the  lymphatics  in  the  capsule  of  the  liver  drain  toward  the  porta; 
others  enter  the  diaphragm. 

The  nerves  are  chiefly  non-medullated  fibers  from  the  sympathetic 
system,  but  the  liver  also  receives  branches  from  the  vagus.  These 
nerves  are  principally  distributed  to  the  blood  vessels,  but  some  are  said 
to  penetrate  the  lobules  and  end  in  contact  with  the  hepatic  cells. 


FIG.  282. — SECTION   OF  THE  LIVER  PREPARED  BY  THE  BIEL- 
SCHOWSKY  METHOD.     X  300. 


288 


HISTOLOGY 


The  interlobular  ducts  are  lined  with  simple  columnar  or  cuboidal 
epithelium.  They  anastomose  with  one  another,  and  have  blind  pockets; 
in  the  larger  ducts,  there  are  branched  mucous  glands.  The  connection 
between  the  ducts  and  the  hepatic  trabeculae  is  difficult  to  observe,  and  it 
was  once  thought  that  the  ducts  with  their  ramifications  produced  the  bile, 
leaving  the  parenchyma  for  the  function  of  internal  secretion.  Through 
injections,  however,  or  by  using  the  Golgi  method,  the  connections  between 
the  bile  capillaries  and  the  bile  ducts  can  be  readily  demonstrated  (Fig. 
283).  They  are  found  at  the  periphery  of  the  portal  canals,  and  were 


Branch  of  portal 
vein. 


Small  interlobu- 
lar bile-duct, 
continuing  in 
bile  capillaries. 


Large    interlobu- 
lar bile-duct. 


Branch  of  hepat- 
ic artery. 


Bile  capillaries.  " 


Wall  of  the  central  vein. 
FIG.  283. — GOLGI  PREPARATION  OF  THE  LIVER  OF  A  DOG.     X240. 

described  histologiqally  by  Hering  (Strieker's  Handbuch,  Leipzig,.  1871). 
On  the  side  toward  the  connective  tissue  these  "canals  of  Hering,"  or 
periportal  ducts,  exhibit  a  flat  or  cuboidal  epithelium,  like  that  of  ordinary 
ducts;  but  toward  the  lobule  they  are  bounded  by  hepatic  cells,  or  by  flat 
cells  interrupted  by  hepatic  cells  (Fig.  284).  Thus  the  hepatic  trabeculae 
are  directly  inserted  into  the  walls  of  the  ducts,  and  the  bile  capillaries  con- 
nect with  the  lumen. 

The  hepatic,  cystic  and  common  bile  ducts  all  have  a  simple  columnar 
epithelium,  with  occasional  goblet  cells  and  branching  mucous  glands. 
Around  the  hepatic  duct  there  is  a  wide  zone  formed  by  the  ramifying 
ducts  of  these  mucous  glands,  as  they  extend  into  the  surrounding  con- 
nective tissue.  The  connective  tissue  layer  is  said  to  contain  many  elastic 


LIVER 


289 


fibers.  It  is  followed  by  a  tunica  muscularis  consisting  chiefly  of  circular 
fibers.  These  form  a  sphincter  around  the  common  bile  duct,  at  the  duo- 
denal papilla.  In  the  cystic  duct  there  are  folds  of  mucous  membrane,  con- 
taining muscle  fibers,  and  forming  the  "spiral  valve." 

The  gall  bladder  is  lined  with  a  folded 
mucous  membrane  covered  with  tall  epi- 
thelial cells  similar  to  those  of  the  intes- 
tine (Fig.  285).  They  have  elongated 
basal  nuclei  and  secretory  granules 
(mucin)  in  the  outer  part  of  their  proto- 
plasm. The  free  surface  is  covered 
with  a  distinct  cuticular  border,  and 
terminal  bars  have  been  observed. 

Goblet  cells  are  absent  and  glands  are  infrequent.  The  muscularis  con- 
sists of  obliquely  circular  fibers  arranged  in  a  plexiform  layer.  Among 
them  are  groups  of  sympathetic  nerve  cells  which  supply  the  muscle,  and 
medullated  fibers  which  end  in  the  epithelium.  The  subserous  tissue  is 
highly  developed  and  contains  large  lymphatic  vessels. 


FIG.  284. — THE  CONNECTION  BETWEEN  BILB 
CAPILLARIES  AND  BILE  DUCTS  IN  A- HUMAN 
EMBRYO  OF  POUR  AND  A  HALF  MONTHS. 
(After  Toldt  and  Zuckerkandl.) 

b.  c.,  Bile  capillary;  h.  c.,  hepatic  cell;  p.  d., 
periportal  duct. 


Muscularis. 

ill 


Tunica 
propria. 


FIG.  285. — FROM  A  SECTION  OF  THE  GALL  BLADDER  OF  AN  ADULT,  A.     X  100.     B,  the  portion  x  of  A. 

X  560. 


PANCREAS. 

Development  and  General  Features.  Although  the  pancreas  in  the  adult 
is  a  single  gland,  it  arises  in  the  embryo  as  two  entirely  distinct  entodermal 
outgrowths,  known  as  the  dorsal  and  ventral  pancreases  respectively. 
The  dorsal  pancreas  grows  out  from  the  dorsal  wall  of  the  intestinal  tube,  a 
little  below  the  level  of  the  common  bile  duct  in  most  mammals,  but  a  little 
above  it  in  man.  The  ventral  pancreas  grows  down  from  the  common  bile 
duct  at  its  junction  with  the  intestinal  tube.  As  seen  in  Fig.  286,  A  and  B, 
the  ventral  pancreas  may  be  more  or  less  bi-lobed.  Usually  it  grows  to 
the  right  of  the  intestine  and  there  meets  the  dorsal  pancreas,  which  ap- 
proaches it  in  close  relation  with  the  portal  vein. 
19 


290 


HISTOLOGY 


The  left  lobe  of  the  ventral  pancreas  sometimes  grows  around  the  left  side  of  the 
intestine  and  joins  the  dorsal  pancreas,  so  that  the  intestine  is  encircled  by  pancreatic 
tissue  (annular  pancreas);  sometimes  it  grows  out  beneath  the  gall  bladder  where  it 
ends  in  a  cystic  enlargement,  as  has  been  observed  in  adult  cats  (cf .  Amer.  Journ.  Anat., 
1912,  vol.  12,  pp.  389-400).  Usually  the  left  lobe  is  scarcely  indicated.  As  a  rather  fre- 
quent abnormality,  accessory  pancreases  of  small  size,  but  sometimes  of  very  typical 


D.  ch. 


P.  d. 


L.  d. 


L.s. 


Int. 


P.  d. 


L.  d. 


Pr.  v. 


D.  ch. 


L.  s. 


Int. 


A  B 

FIG  286. — MODELS  o*  THE  VENTRAL  PANCREAS  IN  PIG  EMBRYOS.     X  120. 

A,  5.1  mm.,  B,  6.0  mm.     D.  ch.,  ducttu  choledochus;  Int.,  intestine;  L.  d.,  right  lobe,  and  L.  s.,  left  lobe  of 
the  ventral  pancreas;  P.  d.,  dorsal  pancreas;  Pr.  v.,  ventral  process  of  the  dorsal  pancreas. 

structure,  are  found  along  the  intestine,  or  even  in  the  wall  of  the  stomach,  especially 
at  the  constriction  between  its  cardiac  and  pyloric  portions.  Such  glands  may  or  may 
not  extend  through  the  tunica  muscularis. 

After  the  dorsal  and  ventral  pancreases  have  come  in  contact,  they  are 
related  to  one  another  as  shown  in  Fig.  287,  A.     The  dorsal  pancreas  is 

much  larger  than  the 
ventral  pancreas,  and 
it  grows  across  the 
body  toward  the  left 
until  it  reaches  the 
spleen.  Thus  it  gives 
rise  to  the  body  and 
tail  of  the  pancreas 
of  the  adult;  and  it 
forms  also  the  ventral 
part  of  the  head  of 
the  gland,  which  fills 
the  concavity  in  the 
duodenal  loop.  In 

the  adult  its  duct  opens  into  the  duodenum  1-3  cm.  above  the  orifice  of  the 
common  bile  duct,  but  it  has  been  tapped  by  an  anastomosis  with  the  ventral 
pancreas.  Its  outlet  persists  as  the  accessory  pancreatic  duct,  discovered  by 
Santorini  (1775).  It  is  shown  in  the  dissection,  Fig.  287,  B,  but  a  large 


FIG.  287. — A,  DIAGRAM  OF  THE  PANCREAS  FROM  A  IS-MM.  HUMAN  EM- 
BRYO. B,  DISSECTION  OF  THE  DUODENUM  AND  PANCREAS  OF  AN 
ADULT.  (After  Schirmer.) 

a.  p.  d.,  Accessory  pancreatic  duct;  c.  d.,  cystic  duct;  d.,  duodenum;  d.  c., 
ductus  ctupledochus;  d.  p.,  dorsal  pancreas;  h.  d.,  hepatic  duct;  p.,  duo- 
denal papilla;  p.  d.,  pancreatic  duct;  St.,  stomach;  v.  p.,  ventral  pan- 


PANCREAS 


291 


branch  ordinarily  found  descending  from  it  in  front  of  the  pancreatic  duct, 
p.  d.,  is  not  included.  In  some  cases  the  accessory  duct  becomes  imper- 
vious, but  it  is  generally  functional,  and  if  the  outlet  of  the  main  duct  were 
blocked  by  gall-stones  or  otherwise,  the  presence  of  this  accessory  duct 
would  be  of  considerable  importance.  In  some  mammals,  as  in  the  pig,  it 
is  normally  the  chief  duct. 

The  duct  of  the  ventral  pancreas  either  opens  into  the  duodenum  close 
beside  the  common  bile  duct  (Fig.  287,  B),  or  it  retains  its  embryonic  rela- 
tion (Fig.  287,  A)  and  opens  into  the  common  bile  duct  near  its  duodenal 
orifice.  The  duct  of  the  ventral 
pancreas,  by  an  anastomosis 
with  the  duct  of  the  dorsal  pan- 
creas, becomes  the  outlet  of  the 
main  pancreatic  duct,  which  was 
first  figured  by  Wirsung  (1642). 
It  will  be  noted  that  a  large  part 
of  the  dorsal  pancreatic  duct, 
extending  through  the  body  and 
tail,  becomes  incorporated  in 
this  main  duct  of  Wirsung;  the 
ventral  pancreas  supplies  only 
its  outlet. 

In  the  adult  no  histological 
distinction  has  ever  been  found 
between  the  two  pancreases, 
but  although  alike  in  structure 

.      .                       .             .  FIG.  288. — SECTION  OF  HUMAN  PANCREAS,  SHOWING  SEV- 

and    Close    together,   there  IS  nO  ERAL  ISLANDS.     (Radasch.) 

i                                          -i  a,  Interlobular  connective  tissue  containing  an  interlobu- 

general      anaStOmOSIS      between  lar  duct,  c ;  b,  capillary ;  d,  interlobular  duct;  e,  alveoli; 

,                   -r»          i       ..i                        •  f,  pancreatic  island. 

them.  Rarely  they  remain  en- 
tirely separate.  Usually,  on  injecting  the  ducts,  only  one  connection  is 
found  between  the  dorsal  and  ventral  pancreases,  but  in  an  abnormal  case 
two  connections  have  been  observed.  Moreover,  anastomoses  between 
the  smaller  ducts  and  tubules  in  the  separate  glands  have  not  been  found 
in  human  adults.  Rings  of  pancreatic  tissue  occur  in  the  embryo,  and  in 
adult  guinea-pigs  Bensley  has  demonstrated  a  free  anastomosis  of  the 
ducts  (Amer.  Journ.  Anat.,  1911,  vol.  12,  pp.  297-388);  such  a  condition 
has  not  yet  been  found  in  man. 

Microscopic  structure.  As  a  whole  the  pancreas  somewhat  resembles  the 
parotid  gland.  It  is  divided  into  lobes  and  lobules  by  connective  tissue 
septa  containing  blood  and  lymphatic  vessels,  nerves,  and  interlobular 
ducts  (Fig.  288).  The  lobules  are  composed  chiefly  of  short  tubules,  or 
alveoli,  which  in  models  appear  pear-shaped',  in  sections  they  are  cut 
at  all  possible  angles.  Instead  of  exhibiting  a  well-defined  %lumen,  the 


2Q2 


HISTOLOGY 


alveoli  appear  to  be  clogged  with  cells,  known  as  centra- alveolar  cells  (or 
centro-acinal  cells).  Irregularly  distributed  among  the  alveoli  there  are 
round  areas  of  paler  cells,  peculiar  to  the  pancreas  (Fig. -288).  They  may 
be  at  the  center  or  periphery  of  the  lobule,  or  occasionally  in  the  inter- 
lobular  connective  tissue.  These  important  structures  were  first  described 
in  Langerhans'  thesis  in  1869  (Inaug.  Diss.,  Berlin),  and  are  known  as  the 
pancreatic  islands  (islands  of  Langerhans). 

The  alveoli  are  composed  chiefly  of  the  secreting  pancreatic  cells  (Fig. 
289).  Toward  the  lumen  their  protoplasm  contains  coarse  granules  of 
zymogen,  which  accumulate  while  the  cell  is  inactive  and  are  eliminated 
during  secretion.  Apparently  they  are  transformed  into  fluid  as  they 


Cells  of 
the  al- 
veolus. 


Inter-  Inter- 

calated  calated 

duct.  duct. 


^-^  Centro-alveolar  cells.    ; 

Zymogen  granules. 
A  B 

FIG.  289. — FROM  SECTIONS  OF  A  HUMAN  PANCREAS.     X  500. 


In  section  A  the  granules  are  wanting,  the  centro-alveolar  cells  are  flat  and  dark;  in  section  B  the  granules 
are  distinct,  the  centro-alveolar  cells  are  cuboidal  and  clear. 

are  discharged,  for  they  are  not  found  free  in  the  intestine.  In  fresh 
specimens  the  granules  are  refractive  and  easily  seen,  but  in  preserved 
tissue  they  are  readily  destroyed,  so  that  the  granular  zone  appears  reticu- 
lar.  The  granules  are  soluble  in  water,  and  are  darkened  by  osmic  acid. 
The  basal  protoplasm  of  the  pancreatic  cells  is  vertically  striated. 
It  contains  the  round  nucleus  which  has  coarse  masses  of  chromatin. 
Within  the  pancreatic  cells  there  have  been  found  "paranuclei"  of  un- 
known nature,  thought  to  be  functionally  important.  After  the  discharge 
of  secretion  the  cells  become  smaller  and  their  boundaries  more  distinct. 
The  pancreatic  cells  rest  upon  basement  membranes  containing  "basket 
cells." 

The  centro-alveolar  cells  may  be  darker  or  lighter  than  the  pancreatic 
cells  (Fig.  289),  but  they  are  always  smaller,  and  may  be  readily  identified 
from  their  central  position.  They  do  not  contain  zymogen  granules. 
The  intralobular  intercalated  ducts,  which  connect  with  the  alveoli,  are 
very  slender,  and  their  walls  are  formed  of  flat  cells  (Fig.  289,  A).  They 


PANCREAS 


293 


terminate  in  clusters  of  alveoli,  which  often  present  clover-leaf  forms. 
The  centro-alveolar  cells  have  been  interpreted  as  due  to  the  invagination 
of  these  ducts  into  the  alveoli,  but  apparently  they  do  not  develop  in  this 
way;  they  are  formed  as  an  inner  stratum  of  a  two-layered  epithelium. 
The  secretory  capillaries  of  the  alveoli  are  shown  in  Fig.  290.  They  ex- 
tend between  the  centro-alveolar  cells  to  the  pancreatic  cells,  and  may  be 
prolonged  between  the  latter,  biit  they  do  not  reach  the  basement 
membrane. 

The  intercalated  ducts  pass  into  excretory  ducts  lined  with  cuboidal 
epithelium,  without  the  intervention  of  secretory  ducts  such  as  are  found 
in  the  salivary  glands.  The  plan  of  the  pancreatic  ducts  is  shown  in 
Fig.  291.  The  main  pancreatic  and  accessory  pancreatic  ducts  are  com- 
posed of  simple  columnar  epithelium  surrounded  by  a  connective  tissue 


Intercellular 
secretory  , 
capillary. 

FIG.  290. — A,  FROM  A  SECTION  OF  THE  PANCREAS  OF  AN  ADULT  MAN.  X  320.  B,  AN  INTERPRETATION  OF 

THE  RIGHT  LOWER  PORTION  OF  A. 

layer,  outside  of  which  is  a  zone  of  circular  smooth  muscle  fibers.  The 
latter  are  gathered  into  sphincters  at  the  major  and  minor  duodenal 
papillae,  where  the  ducts  open.  Occasional  goblet  cells  and  small  glands 
resembling  mucous  glands  have  been  found  in  the  mucosa  of  the  large 
ducts. 

The  blood  and  lymphatic  vessels  and  nerves  of  the  pancreas  resemble 
those  of  the  salivary  glands.  The  capillaries  have  notably  wide  meshes 
so  that  considerable  portions  of  the  alveoli  are  not  in  contact  with  them. 
The  nerves  end  around  the  blood  vessels,  ducts  and  pancreatic  cells. 
They  are  chiefly  non-medullated  sympathetic  fibers  from  the  cceliac 
plexus,  associated  with  scattered  nerve  cells  found  within  the  pancreas. 
Lamellar  corpuscles  occur  in  the  connective  tissue. 

The  pancreatic  islands  are  usually  not  to  be  found  in  human  embryos 
under  50  mm.  in  length.  Thus  they  develop  only  after  the  pancreatic 
glands  have  come  together  and  attained  considerable  size.  They  arise  as 
outgrowths  from  the  smaller  ducts,  with  which  they  may  retain  a  solid 
stalk-like  connection,  or  they  may  become  wholly  detached.  According 
to  Bensley,  detached  islands  in  the  guinea-pig  are  infrequent.  In  the 


2Q4 


HISTOLOGY 


embryo,  as  in  the  adult  (Fig.  292),  they  consist  of  coiled  anastomosing 
cords  of  cells,  or  irregular  masses,  which  are  in  close  relation  with  the 
endothelium  of  dilated  capillary  blood  vessels.  The  islands  are  composed 
of  pale  cells  with  very  delicate  cell  walls,  and  they  contain  finer  granules 
than  those  in  the  pancreatic  cells.  In  fresh  preparations  Bensley  ob- 
served that  these  granules  exhibit  the  Brownian  movement,  and  that 
colorless  spaces  occur  among  them,  representing  the  canals  of  Holmgren's 
trophospongium.  When  preserved  by  special  methods,  two  forms  of 
island-cells  may  be  distinguished  by  the  staining  reactions  of  their  gran- 


-^  Alveoli. 


Tubule. 
FIG.  291. — DIAGRAM  OF  THE  PANCREAS. 


FIG.  292. — AN  ISLAND  OF  THE  PANCREAS  WITH  THE  SUR- 
ROUNDING ALVEOLI,  FROM  AN  ADULT.     X  400. 


ules.  In  one  type  of  cell  the  nucleus  is  oval,  with  finely  granular  chro- 
•  matin;  and  in  the  other  it  is  round,  with  large  chromatin  granules.  Having 
neither  ducts  nor  lumen,  the  islands  produce  an  internal  secretion,  which 
is  received  by  the  blood  vessels.  There  is  evidence  that  this  secretion 
plays  an  important  part  in  carbohydrate  metabolism.  If  the  pancreas 
is  removed,  sugar  appears  in  the  urine;  but  if  the  ducts  of  the  pancreas 
are  tied,  the  pancreatic  alveoli  degenerate,  leaving  the  islands  functional, 
and  sugar  is  not  found  in  the  urine.  Thus  the  islands  are  regarded  as 
physiologically  distinct  from  the  remainder  of  the  pancreas. 

Morphologically  the  islands  are  likewise  distinct,  and  Bensley  finds 
that  the  possibility  of  the  transformation  of  alveolar  tissue  into  island 
tissue,  or  conversely  of  island  tissue  into  alveolar  tissue,  "has  not  a  single 
well-established  fact  to  support  it"  (Amer.  Journ.  Anat.,  1911,  vol.  12,  pp. 
297-388).  The  number  of  islands,  however,  is  subject  to  great  variation, 


PANCREAS 


295 


there  being  from  13,000  to  56,000  in  the  entire  pancreas  of  guinea-pigs 
(Bensley),  the  average  being  twenty-two  islands  per  cubic  millimeter.  In 
all  stages,  both  in  the  guinea-pig  and  in  inan,  they  are  usually  most  numer- 
ous in  the  tail  of  the  pancreas,  and  least  numerous  in  its  head  (Opie,  Johns 
Hopkins Hosp.  Bull.,  1900,  vol.  n,  pp.  205-209). 


RESPIRATORY  APPARATUS. 

Development.  The  respiratory  apparatus,  consisting  of  the  larynx, 
trachea,  bronchi,  and  langs,  arises  as  a  median  ventral  outgrowth  of  the 
fore-gut,  immediately  behind  the  last  pharyngeal  pouches.  It  apparently 
is  in  no  way  related  to  the  branchial  pouches,  but  it  may  correspond  with 
the  air-bladder  of  the  bony  fishes.  At 
the  stage  when  the  lung-bud  develops, 
the  fore-gut  is  laterally  flattened,  so  that 
its  lumen  is  a  dorso-ventral  cleft.  The 
lung-bud  develops  as  a  pear-shaped  swell- 
ing, directed  downward,  on  the  ventral 
border  of  the  fore-gut;  and  this  swelling 
becomes  split  off,  from  below  upward,  to 
form  the  trachea,  which  is  at  first  short 
but  which  rapidly  elongates.  The  upper 
end  of  the  trachea,  with  the  cartilages 
which  develop  around  it,  constitutes  the 
larynx.  At  the  lower  end  of  the  trachea, 
the  pyriform  dilatation  spreads  out  on 
either  side  to  form  the  primary  bronchi 
(Fig.  293,  A). 

The  tracheal  and  bronchial  tubes  are  lodged  in  a  mass  of  connective 
tissue,  situated  above  and  behind  the  pericardial  cavity,  and  since  this 
tissue  stands  in  the  middle  of  the  thorax  it  is  known  as  the  mediastinum. 
It  is  comparable  with  a  broad  mesentery.  As  the  bronchi  push  out  later- 
ally they  occupy  right  and  left  folds  bulging  from  the  mediastinum,  called 
by  Ravn  the  pulmonary  wings  (alee  pulmonales}.  Into  these  the  bronchi 
extend  and  produce  branches  after  the  manner  of  a  gland  (Fig.  293,  B). 
The  pulmonary  wings  consist  of  mesenchyma,  covered  by  the  epithelium 
which  lines  the  body  cavity.  At  first  they  project  into  the  part  of  the  body 
cavity  which  connects  the  peritoneal  with  the  pericardial  cavity;  later,  by 
the  development  of  the  pleuro-pericardial  and  pleuro-peritoneal  membranes 
respectively  (the  latter  being  a  part  of  the  diaphragm)  the  chamber  into 
which  the  pulmonary  wings  project  is  entirely  cut  off  from  the  rest  of  the 
body  cavity.  On  either  side,  it  forms  a  pleural  cavity  (see  Fig.  169,  p. 
175).  The  epithelium  and  underlying  connective  tissue  covering  the  pul- 


FIG.  293. — RECONSTRUCTIONS  OF  THE 
LUNGS  OF  YOUNG  EMBRYOS,  SEEN  FROM 
THE  VENTRAL  SURFACE.  (His.) 

A,  A  younger  stage  than  B;  ep,  apical 
bronchus;  I,  II,  primary  bronchi. 


2g6  HISTOLOGY 

monary-wings,  constitute  the  visceral  pleura;  and  the  similar  layers  toward 
the  thoracic  wall  form  the  parietal  pleura.  These  layers  are  comparable 
in  development  and  structure  with  the  corresponding  layers  of  the  peri- 
toneum. Other  subdivisions  of  the  pleura  are  the  mediastinal,  pericardial, 
and  diaphragmatic  pleurae.  The  lung  is  connected  with  the  mediastinum 
by  a  short  and  broad  stem  of  connective  tissue,  across  which  the  bronchi, 
vessels  and  nerves  extend.  This  is  the  root  of  the  lung,  and  the  vessels 
enter  at  the  hilus. 

The  branches  which  are  given  off  by  the  stem-bronchus  within  the  pulmonary 
wings,  are  formed  with  great  regularity,  and  they  have  been  carefully  studied  in  many 
mammals.  Very  early  in  development,  the  human  lungs  become  asymmetrical,  and 
at  the  stage  shown  in  Fig.  293,  B,  the  three  lobes  of  the  right  lung  and  the  two  lobes 
of  the  left  lung  are  already  indicated.  In  the  pig  the  asymmetry  is  greater,  since  on  the 
right  an  unpaired  lobe  proceeds  directly  from  the  trachea;  in  certain  animals,  as  in  the 
seal,  the  right  and  left  lungs  have  symmetrical  bronchi.  Whether  the  symmetrical 
condition  is  the  primary  one,  and  how  the  bronchi  of  one  lung  should  be  homologized 
with  those  of  the  other,  are  questions  which  have  been  much  discussed.  For  the  com- 
parative anatomy  of  the  bronchi,  see  Huntington,  Ann.  N.  Y.  Acad.  Sci.,  1898,  vol.  n, 
pp..  127-148;  for  their  development,  especially  in  the  pig,  see  Flint,  Amer.  Journ. 
Anat.,  1906,  vol.  6,  pp.  1-137. 

The  blood  vessels  of  the  lungs  are  derived  from  several  sources.  They 
include  the  large  pulmonary  arteries  and  veins,  which  are  the  principal 
vessels  of  the  lung,  and  the  small  but  important  bronchial  arteries  and  veins. 
The  pulmonary  vessels  are  shown  in  Fig.  294,  which  represents  the  trachea 
and  right  lung  of  a  human  embryo,  seen  from  the  left  side;  the  left  lung  has 
been  cut  away  at  /.  br. 

The  pulmonary  arteries  develop  in  connection  with  the  pulmonary 
arches ,  which  are  two  vessels,  one  on  either  side,  passing  from  the  ventral 
aorta  to  the  dorsal  aorta. '  Approximately  midway  in  its  course,  each  of 
these  arches  sends  a  branch  to  the  lung  of  the  corresponding  side.  Subse- 
quently the  trunk  of  the  ventral  aorta  becomes  spirally  subdivided  by  a  sep- 
tum, so  that  the  portion  leading1  to  the  pulmonary  arches  is  split  off  from 
the  rest;  the  way  in  which  its  root  becomes  connected  with  the  right 
ventricle  only,  has  been  described  with  the  development  of  the  heart.  As 
a  result  of  this  subdivision,  the  pulmonary  artery  leaves  the  heart  and  di- 
vides into  right  and  left  arches,  each  of  which  sends  a  branch  to  the  lung  on 
the  same  side  and  then  passes  on  to  the  dorsal  aorta.  The  connection  be- 
tween the  right  arch  and  the  right  dorsal  aorta  is  soon  lost,  however,  so  that 
the  vessel  to  the  right  lung  (Fig.  294,  r.  r.)  appears  to  be  given  off  from  the 
main  pulmonary  artery.  The  left  pulmonary  arch  enlarges,  and  until  birth 
it  forms  a  great  vessel,  known  as  the  ductus  arteriosus,  which  conveys  most 
of  the  blood  from  the  pulmonary  artery  into  the  aorta.  The  amount  of 
blood  which  goes  to  the  inactive  lungs  may  be  inferred  from  the  relative 
size  of  the  vessels  shown  in  the  figure.  Soon  after  birth,  when  respiration 


RESPIRATORY    APPARATUS 


297 


has  begun,  the  ductus  arteriosus  closes,  becoming  a  fibrous  cord,  and  then 
the  volume  of  blood  going  through  the  pulmonary  artery  equals  that  in  the 
aorta.  (For  further  details  regarding  the  development  of  the  pulmonary 
arteries,  see  Bremer,  Amer.  Journ.  Anat,  1902,  vol.  i,  pp.  137-144). 

The  pulmonary  veins  are  at  first  represented  by  a  capillary  plexus 
around  the  lung-bud,  which  receives  its  blood  in  part  from  the  pulmon- 
ary arteries  already  described,  and  in  part  from 
branches  of  the  dorsal  aorta,  some  of  which 
persist  as  the  bronchial  arteries.  The  capillary 
plexus  is  drained  partly  by  branches  of  the 
posterior  cardinal  or  azygos  veins,  representing 
the  future  bronchial  veins,  and  partly  by  a 
minute  vein  which  has  grown  out  from  the  left 
atrium  and  is  destined  to  become  the  great 
pulmonary  veins.  At  a  certain  stage  these 
veins,  two  from  each  lung,  have  a  common 
orifice  in  the  left  atrium;  but  in  later  stages,  as 
the  heart  enlarges,  their  short  common  stem  is 
taken  up  into  the  wall  of  the  atrium,  so  that 
the  four  pulmonary  veins  acquire  separate 
openings.  The  early  stages  in  the  development 
of  the  pulmonary  veins  in  the  cat  have  recently 
been  studied  by  Brown  (Anat.  Rec.,  1913,  vol. 
7,  pp.  299-330). 

The  small  bronchial  arteries,  one  or  two  on 
each  side,  are  branches  of  the  upper  part  of  the 
thoracic  aorta  (Fig.  294);  sometimes  one  of 
them  proceeds  from  an  intercostal  artery. 
The  bronchial  arteries  enter  the  hilus  of  the 
lung  and  pass  into  the  fibrous  tissue  in  the  walls 
of  the  bronchi.  The  main  stems  branch  with 
,  the  bronchi.  They  produce  capillary  net- 
works in  the  bronchial  mucous  membrane,  and  send  branches  to  the  peri- 
bronchial  connective  tissue,  supplying  it  with  capillaries  and  becoming 
the^yasa^^agorum  of  the  main  branches  of  the  pulmonary  artery  (Miller, 
Anat.  Anz.,  1906,  vol.  28,  pp.  432-436).  In  some  animals  Miller  finds 
that  the  bronchial  arteries  pass  on  into  the  pleura,  as  in  the  horse;  in  others, 
like  the  dog,  terminal  branches  of  the  pulmonary  arteries  supply  the  pleura; 
and  in  the  human  lung  the  pleura  receives  both  pulmonary  and  bronchial 
vessels  (Amer.  Journ.  Anat.,  1907,  vol.  7,  pp.  389-407). 
.  The  bronchial  veins  are  small  branches  of  the  azygos  vein.  They  do 
not  receive  all  the  blood  from  the  bronchial  arteries,  since  some  capillaries 
from  the  latter  are  drained  by  the  pulmonary  veins. 


th.ao, 


s.t 


FIG.  294. — RECONSTRUCTION  OF  A 
PART  OF  A  HUMAN  EMBRYO  OF 
13.8  MM.  (Dr.  F.  W.  Thyng.) 

ao.,  Aorta;  d.a.,  ductus  arteriosus; 
L,  entodermal  part  of  the  lung; 
1.  at.,  left  atrium;  1.  br.,  left 
bronchus;  1.  r.,  left  ramus  of 
pulmonary  artery,  p.  a.;  r.  r., 
its  right  ramus;  oe.,  oesopha- 
gus; p.  c.,  pericardia!  cavity; 
p.  v.,  pulmonary  vein;  s.  t., 
septum  transversum;  th.  ao., 
thoracic  aorta;  tr.,  trachea. 


2Q8  HISTOLOGY 

LARYNX. 

The  mucous  membrane  of  the  larynx  is  a  continuation  of  that  of  the 
pharynx,  and  accordingly  consists  of  epithelium  and  tunica  propria.  A 
submucosa  connects  it  with  the  underlying  parts.  In  most  places  the 
epithelium  appears  to  be  stratified  and  columnar,  but  it  is  said  to  be 
£>seudo-stratified,  with  nuclei  at  several  levels  (Fig.  38,  p.  49).  It  is 
difficult  to  determine  whether  or  not  all  the  cells  are  in  contact  with  the 
basement  membrane.  This  type  of  epithelium,  which  occurs  also  in  the 
trachea,  is  ciliated.  The  stroke  of  the  cilia  is  toward  the  pharynx.  A 
stratified  epithelium  with  squamous,  non-ciliated  outer  cells  is  found  on 
the  vocal  folds  (true  vocal  cords),  on  the  anterior  surface  of  the  arytsenoid 
cartilages  and  on  the  laryngeal  surface  of  the  epiglottis.  The  distribution 
of  the  two  sorts  of  epithelium  above  the  vocal  folds  is  subject  to  individual 
variation.  The  squamous  epithelium  often  occurs  in  islands.  The  tunica 
propria  is  composed  of  fibrous  connective  tissue  with  many  elastic  fibers, 
and  beneath  the  epithelium  it  forms  a  basement  membrane  (membrana 
propria).  It  includes  reticular  tissue  containing  a  variable  number  of 
lymphocytes,  which  are  gathered  in  solitary  nodules  in  the  wall  of  the 
laryngeal  ventricle  (sinus  of  Morgagni).  Connective  tissue  papillae  are 
found  chiefly  beneath  the  squamous  epithelium.  At  the  free  border  of  the 
vocal  folds  and  on  their  under  surface,  the  papillae  unite  to  form  longitud- 
inal ridges.  On  the  laryngeal  surface  of  the  epiglottis  there  are  only 
isolated  papillae,  against  which  rest  the  short  taste  buds. 

The  submucosa  contains  mixed,  branched,  tubulo-alveolar  glands, 
measuring  from  0.2  to  i.o  mm.;  they  are  abundant  in  the  ventricular 
folds  but  are  absent  from  the  middle  part  of  the  vocal  folds.  The 
ventricular  folds  (false  vocal  cords)  consist  of  a  loose  vascular  fatty  tissue, 
often  containing  small  bits  of  elastic  cartilage  about  i  mm.  long,  and 
similar  cartilages  measuring  2-3 . 5  mm.  are  sometimes  found  in  the  anterior 
ends  of  the  vocal  folds. 

The  cartilages  of  the  larynx  are  mostly  of  the  hyaline  variety,  resem- 
bling those  of  the  ribs.  To  this  class  belong  the  thyreoid,  cricoid,  the 
greater  part  of  the  arytaenoid,  and  often  the  small  triticeous  cartilages. 
Elastic  cartilage  is  found  in  the  epiglottis,  the  cuneiform  and  corniculate 
cartilages,  the  apex  and  vocal  process  of  the  arytsenoids,  and  generally  the 
median  part  of  the  thyreoid.  In  women  this  portion  is  not  involved  in 
the  ossification  (chiefly  endochondral)  which  begins  in  the  thyreoid  and 
cricoid  cartilages  between  the  twentieth  and  thirtieth  years.  The  tri- 
ticeous cartilages  (nodules  in  the  lateral  hyothyreoid  ligaments,  named 
from  their  resemblance  to  grains  of  wheat)  are  sometimes  composed  of 
fibro-cartilage. 

The  blood  vessels  form  two  or  three  networks  parallel  with  the  surface, 


RESPIRATORY   APPARATUS  2 99 

followed  by  a  capillary  plexus  just  beneath  the  epithelium.  The  lym- 
phatic vessels  similarly  form  two  communicating  networks,  of  which  the 
more  superficial  consists  of  smaller  vessels  and  is  situated  beneath  the 
capillary  plexus.  The  nerves  form  a  deep  and  a  superficial  plexus  which 
are  associated  with  microscopic  ganglia.  Non-medullated  fibers  end  either 
beneath  the  epithelium  in  bulbs  and  free  endings  with  terminal  knobs,  or 
within  the  epithelium  in  free  ramifications  and  in  taste  buds.  Below  the 
vocal  folds,  subepithelial  nerve  endings  and  buds  are  absent,  but  many 
intraepithelial  fibers  occur,  which  surround  individual  taste  cells.  The 
nerves  and  vessels  of  the  larynx  are  numerous,  except  in  the  dense  elastic 
tissue  of  the  vocal  folds. 


TRACHEA  AND  BRONCHI. 

The  trachea  consists  of  a  mucosa,  submucosa,  and  a  fibrous  outer 
layer  containing  the  tracheal  cartilages.  The  general  arrangement  of 
the  layers  is  the  same  as  that  found  in  the  large  bronchi  (Fig.  295). 

The  mucosa  consists  of  pseudo-stratified  columnar  epithelium  with 
cilia  proceeding  from  distinct  basal  bodies  (Fig.  38,  p.  49).  Exception- 
ally, the  lining  of  the  trachea,  toward  the  oesophagus,  has  been  found  to 
consist  of  stratified  squamous  epithelium  resting  on  connective  tissue 
papillae.  Beneath  the  epithelium  there  is  a  broad  basement  membrane, 
followed^  by  a  layer  of  reticular  tissue  containing  many  lymphocytes, 
forming  a  tunica  propria.  Beneath  the  reticular  tissue  there  is  a  layer  of 
coarse  longitudinal  elastic  fibers,  which  may  readily  be  seen  in  haema- 
toxylin  and  eosin  preparations.  This  layer  may  be  compared  with  the 
muscularis  mucosas  of  the  intestine. 

The  submucosa  is  a  layer  of  loose  fatty  connective  tissue  extending  to 
the  perichondrium  of  the  tracheal  cartilages.  It  contains  the  bodies  of 
the  tracheal  glands,  which  include  both  serous  and  mucous  cells,  and  are 
beautiful  objects  for  the  study  of  serous  crescents. 

The  outer  layer  of  the  trachea  is  continuous  with  the  tissue  of  the 
mediastinum.  It  contains  abundant  blood  and  lymphatic  vessels,  and 
nerves,  both  medullated  and  non-medullated.  Internally  it  forms  the 
perichondrium  around  the  succession  of  C-shaped  hyaline  cartilages,  the 
free  ends  of  which  are  toward  the  oesophagus.  In  the  intervals  between 
these  ends  there  is  a  layer  of  transverse  smooth  muscle  fibers,  usually 
accompanied  by  outer  longitudinal  fibers.  As  in  the  intestine,  elastic 
fibers  are  abundant  among  the  muscle  cells.  In  old  age,  the  hyaline 
cartilages  show  fibrous  degenerative  changes,  and  may  become  partly 
calcified. 

The  primary  bronchi  have  the  same  structure  as  the  trachea,  but  in 
their  subdivisions  changes  occur,  and  the  C-shaped  rings  of  cartilage  are 


300 


HISTOLOGY 


replaced  by  irregular  plates  found  on  all  sides  of  the  tube  (Fig.  295). 
These  diminish  in  size  as  the  bronchi  become  smaller,  and  disappear  in 
those  about  i  mm.  in  diameter.  Usually  the  cartilages  are  hyaline,  but 
elastic  cartilage  is  said  to  occur  in  places.  The  circular  muscle  fibers 
form  a  layer  completely  surrounding  the  tube  internal  to  the  cartilages. 
Branched  tubulo-alveolar  bronchial  glands  extend  further  down  the  tubes 
than  the  cartilages.  In  the  larger  bronchi  they  are  present  in  great  numbers, 


Tunica  Circular 

Epithelium.  propria.          muscle  fibers 


Alveoli. 


Fat  cells. 


Cartilage.^  ,;' 

""'^•^ 

Connective  tissue. 
Bronchial  gland. 

Duct  of  gland. 


FIG.  295. — CROSS  SECTION  OF  A  BRONCHUS  2  MM.  IN  DIAMETER,  FROM  A  CHILD. 


and  their  bodies  lie  outside  of  the  muscular  layer  and  project  into  the  spaces 
between  the  cartilages.  The  mucosa  is  thrown  into  longitudinal  folds; 
it  is  covered  with  ciliated  epithelium  containing  goblet  cells  and  resembling 
that  of  the  trachea.  Lymphocytes  are  numerous  in  the  tunica  propria, 
sometimes  collecting  in  solitary  nodules  and  wandering  into  the  epithelium. 
The  small  bronchi,  0.5-1.0  mm.  in  diameter,  are  known  as  bronchioles. 
They  are  free  from  cartilage  and  glands,  and  are  lined  throughout  with 
ciliated  columnar  epithelium. 


RESPIRATORY   APPARATUS 


301 


LUNGS. 

The  arrangement  of  the  ultimate  branches  of  a  bronchiole  is  shown  in 
the  diagram,  Fig.  296.  The  respiratory  bronchioles,  0.5  mm.  or  less  in 
diameter,  at  their  beginning  contain  a  simple  columnar  ciliated  epithelium. 
Further  in  their  course  the  goblet  cells  disappear,  cilia  are  lost,  the  cells 
become  cuboidal,  and  among  them  are  found  thin,  non-nucleated  plates  of 
different  sizes.  These  plates  constitute  the  respiratory  epithelium.  The 
transition  from  the  cuboidal  to  the  respiratory  epithelium  occurs  irregu- 
larly, so  that  a  bronchiole  may  have  cuboidal  epithelium  on  one  side  and 


Bronchial  artery.  — 


Pulmonary  vein.  •- 


—  "••  Pulmonary  artery. 


Respiratory  bronchiole. 


Pleural  capillaries. 


(Lobule.) 

FIG.  296. — DIAGRAM  OF  A  LOBULE  OF  THE  LUNG,  SHOWING  THE  BLOOD  VESSELS  AND  THE  TERMINAL 

BRANCHES  OF  A  BRONCHIOLE. 

respiratory  epithelium  on  the  other;  or  one  sort  of  epithelium  may  form  an 
island  in  the  midst  of  the  other.  Hence  the  respiratory  bronchioles 
contain  a  mixed  epithelium  (Fig.  297,  A).  The  respiratory  epithelium 
steadily  gains  in  extent  until  the  cuboidal  epithelium  has  disappeared. 

At  irregular  intervals  along  the  bronchioles  the  respiratory  epithelium 
forms  hemispherical  outpocketings  or  alveoli.  The  alveolar  ducts,  from  i 
to  2  mm.  long,  differ  from  the  respiratory  bronchioles  in  that  they  contain 
only  the  respiratory  epithelium  and  are  thickly  beset  with  alveoli.  The 
layer  of  smooth  muscle  fibers  may  be  traced  to  the  end  of  the  alveolar 
ducts,  where  it  terminates.  Since  the  muscles  do  not  extend  over  the 


302 


HISTOLOGY 


alveoli,  but  merely  surround  the  main  shaft  of  the  duct,  the  layer  is  greatly 
interrupted,  and  some  consider  that  it  ends  in  the  course  of  the  duct. 
The  respiratory  bronchiole  may  be  continued  as  a  single  alveolar  duct  or 
may  divide  into  two  or  more.  The  alveolar  ducts  branch  to  produce  ake- 


Cuboidal 

epithelial        Non-nucleated 
cells.  plates. 


Pores.       Cuboidal  epithelial  cells.    Non-nucleated 

" 


Border  of  an  alveolus. 
FIG.  297.  —  FROM  SECTIONS  OF  THE  HUMAN  LUNG. 


Fundus  of  an  alveolus. 
X  240. 


A,  Mixed  epithelium  of  a  respiratory  bronchiole;  B,  an  alveolus  sketched  with  change  of  focus;  the  border 
of  the  alveolus  is  shaded;  it  is  covered  by  the  same  epithelium  as  that  of  the  (clear)  fundus  of  the 
alveolus;  the  nuclei  of  the  cells  are  invisible.  (Silver  nitrate  preparation.) 

olar  sacs  (inf  undibula)  which  are  cavities  in  the  center  of  clusters  of  alveoli. 
The  sacs  resemble  the  ducts  as  shown  in  Fig.  296. 

According  to  Miller  (Arch.  f.  Anat.  u.  Entw.,  1900,  pp.  197-228)  who  has  made 

careful  reconstructions  of  the  terminal 
branches  in  the  human  lung,  an  atrium,  or 
round  cavity,  should  be  recognized  between 
the  alveolar  duct  and  the  alveolar  sac.  The 
alveolar  duct  is  said  to  terminate  by  open- 
ing into  3  to  6  atria,  the  entrances  to  which 
are  surrounded  by  smooth  muscle  fibers 
forming  "  a  sort  of  sphincter"  ;  the  atria  pos- 
sess no  muscle  fibers.  Each  atrium  is  con- 
nected with  two  or  more  alveolar  sacs,  and 
is  moreover  beset  with  alveoli  (Fig.  298). 
Stohr  states  that  the  recognition  of  an 
atrium  between  the  alveolar  duct  and 
alveolar  sac  seems  to  him  superfluous;  "in 
good  casts  of  the  human  lung  it  is  not  to 
be  distinguished,  and  in  other  animals  it  is 
inconstant." 


FIG.  298. — CAMERA  LUCIDA  DRAWING  FROM  A 
SECTION  OF  A  CALF'S  LUNG.  (Miller.) 

The  stippling  indicates  smooth  muscle  and  cu- 
boidal  epithelium ;  the  lines,  respiratory  epithe- 
lium. B.  R.,  Respiratory  bronchiole;  D.  A., 
alveolar  duct;  A.,  atrium;  A.  S.,  alveolar  sac. 


In  sections,  without  resort  to  reconstructions,  very  little  can  be  found 
out  concerning  the  relations  of  the  alveoli  to  the  bronchial  ramifications. 
The  following  structures  are  all  which  can  easily  be  identified:  (i)  alveoli; 


LUNGS  303 

(2)  spaces  bounded  by  alveoli  (alveolar  sacs,  atria  and  alveolar  ducts,  the 
ducts  having  muscle  fibers  in  their  walls);  (3)  small  bronchioles  having 
scattered  alveoli  along  their  walls,  and  therefore  presenting  a  mixed  epithe- 
lium (respiratory  bronchioles);  and  (4)  bronchioles  with  no  respiratory 
epithelium. 

The  study  of  sections  of  the  adult  lung  is  facilitated  by  comparison 
with  those  from  an  embryonic  lung.  Comparable  sections,  including 
the  pleura,  and  drawn  at  the  same  scale  of  magnification,  are  shown  in 
Figs.  300  and  301.  In  the  lung  of  the  embryo  of  four  months,  the  terminal 
branches  of  the  bronchioles  are  found  in  the  centers  of  lobules,  one  of  which 
is  shown  in  Fig.  300  (bounded  by  b.  v.  and  lym.).  The  axial  bronchioles 
break  up  into  ramifying  tubules  lined  with  cuboidal  cells,  and  at  birth 
the  alveoli  which  are  found  at  the  end  of  these  structures  are  also  lined  with 
cuboidal  epithelium.  The  main  arteries  run  with  the  axial  bronchioles 
in  the  centers  of  lobules;  and  the  large  veins  and  lymphatic  vessels  are  at 
their  periphery.  This  arrangement  is  retained  in  the  adult  (Fig.  296). 
Deep  in  the  lung,  the  small  bronchi  are  surrounded  by  considerable  con- 
nective tissue,  containing  arteries,  veins  and  large  lymphatic  vessels. 

After  respiration  has  been  established,  the  alveoli  become  greatly 
distended,  so  that  the  connective  tissue  containing  the  capillary  vessels 
is  flattened  out  in  very  thin  layers.  These  layers  are  bounded  on  either 
side  by  the  respiratory  epithelium  of  adjacent  alveoli  (Fig.  301).  In 
producing  this  epithelium,  the  cells  not  only  become  flattened  but  they  are 
transformed  into  thin  structureless  plates,  and  those  from  several  cells 
may  fuse  to  form  large  plates.  In  amphibia,  nuclei  in  small  amounts  of 
protoplasm  are  found  attached  to  the  basal  or  connective  tissue  side  of  the 
plates,  often  associated  in  groups.  In  addition  to  these  cells,  the  alveolar 
walls  contain  the  endothelial  cells  of  the  capillaries,  connective  tissue  cells, 
wandering  cells,  and  many  elastic  fibers.  These  fibers  surround  the 
alveoli  and  encircle  their  outlets;  the  alveolar  walls  are  so  elastic  that  in 
inspiration  they  may  expand  to  three  times  the  diameter  to  which  they 
return  during  expiration  (o.i  to  0.3  mm.).  Pores  have  been  described 
leading  from  one  alveolus  to  another  (Fig.  297,  B). 

The  richness  of  the  capillary  network  in  the  alveolar  walls  is  seen  in 
injected  specimens  (Fig.  299).  -Respiration  takes  place  by  the  transfer  of 
gases  between  the  blood  in  these  vessels  and  the  air  in  the  alveoli,  therefore 
through  the  endothelial  cells  and  alveolar  plates,  together  with  the  trivial 
amount  of  connective  tissue  which  may  intervene. 

The  pulmonary  and  bronchial  blood  vessels  have  already  been  de- 
scribed, and  their  relations  to  the  lobule  of  the  lung  are  shown  in  Fig.  296. 
The  pulmonary  arteries  are  axial  vessels  within  the  lobules,  breaking  up  in- 
to terminal  branches  at  the  atria,  and  these  branches  become  axial  along  the 
alveolar  sacs.  Each  terminal  branch  has  been  described  as  the  center  of 


3°4 


HISTOLOGY 


an  ultimate  lobule  or  structural  unit.  The  veins  are  peripheral  both  in 
the  units  and  larger  lobules;  between  the  latter  they  run  through  connec- 
tive tissue  septa. 

The  abundant  lymphatic  vessels  are  arranged  in  a  superficial  set  drain- 
ing into  the  pleura  by  way  of  the  interlobular  septa;  and  a  deep  set  drain- 
ing toward  the  hilus  along  the  bronchi,  accompanying  the  large  vessels. 
Lymphatics  of  the  deep  set  do  not  extend  into  the  lobules;  they  terminate 
along  the  alveolar  ducts.  Around  the  larger  bronchi  and  at  the  root  of  the 
lung,  lymph  glands  are  numerous.  A  conspicuous  feature  of  the  sections 
of  the  lung  is  the  presence  of  black  soot  in  the  tissue  around  the  lymphatic 

vein.  vessels.     It  penetrates  the  pulmo- 

nary  epithelium  in   the   smallest 

Capillaries.        .  .    . 

bronchioles,     apparently    passing 
Artery.          between  the  epithelial  cells.    Some 
of  it  is  taken  up  by  phagocytes. 
Having     entered    the    lymphatic 

FIG.   299.— FROM  A   SECTION  OF  THE  LUNG  OF   A      VCSSels  it  is  distributed  along  their 
CHILD,    INJECTED     THROUGH    THE    PULMONARY  _          .  ,.  .      . 

ARTERY,    x  so.  courses.      On  the  surface  of  the 

Of  the  five  alveoli  drawr^.the^three  upper  ones  are       lung  it  ig    seen  Jn  tfa  interlobular 

septa,  marking  out  the  boundaries 

of  the  lobules.  Because  of  the  steady  increase  in  this  deposit,  the  color 
of  the  lungs  changes  from  birth  until  old  age. 

The  nerves  of  the  lung  include  the  pulmonary  plexus  derived  from  the 
sympathetic  system.  Its  fibers  enter  at  the  root  of  the  lung  and  spread 
around  the  bronchi  and.  vessels,  to  which  they  are  chiefly  distributed. 
Small  ganglia  are  found  within  these  plexuses.  The  vagus  also  sends 
branches  to  the  lungs,  including  mediillated  and  non-medullated  fibers, 
which  join  the  sympathetic  plexuses. 

PLEURA. 

The  visceral  pleura  is  a  thinner  layer  than  the  parietal  pleura,  and  is 
closely  attached  to  the  lung.  It  is  covered  with  a  single  layer  of  flat 
mesothelial  cells,  which  in  the  collapsed  lung  become  thicker  and  shorter. 
In  specimens  which  have  been  handled,  this  layer  is  often  lacking.  It  rests 
upon  a  thin  layer  of  fine-meshed  fibrous  tissue,  beneath  which  is  the  coarse 
subserous  layer  continuous  with  the  interlobular  septa  of  the  lung  (Fig. 
301).  This  tissue  is  highly  elastic.  In  the  .subserous  layer,  blood 
vessels,  derived  from  both  pulmonary  and  bronchial  arteries,  form  an 
abundant  capillary  plexus.  The  superficial  lymphatic  vessels  are  very 
evident,  and  in  relation  with  them  lymphoid  tissue  is  found,  and  occa- 
sionally lymph  nodules.  Stomata,  which  have  been  described,  are  pre- 
sumably artificial  apertures  in  the  epithelium  and  are  not  connected  with 
the  lymphatic  vessels. 


b.v. 


lym. 


3°5 


*..>•"'•  i 


C.t.  S.S. 


FIG.  300. 

lym. 


b.v. 


al.s.       al. 


-V; 


FIG.  301. 

FIGS.  300  AND  301.— SECTIONS  OF  THE  LUNG  DRAWN  ON  THE  SAME  SCALE  OF  MAGNIFICATION:  FIG.  301. 

FROM  A  HUMAN  EMBRYO  OF  FOUR  MONTHS;  FIG.  301,  FROM  AN  ADULT. 
al.,  Alveolus;  al.  s.,  alveolar  sac;  br.,  bronchiole;  b.  v.,  blood  vessel;  c.  t.,  outer  layer  of  pleural  connective 

tissue;  ep.,  pleural  epithelium;  lym.,  lymphatic  vessel;  pi.,  pleura;  s.  s.,subserous  connective  tissue: 

t.  b..  terminal  branch  of  the  bronchiole. 


306 


HISTOLOGY 


"  The  parietal  pleura  is  a  thicker  and  less  elastic  layer.  Ventrally  and 
below,  toward  the  pleuro-pericardial  membrane,  it  exhibits  folds  containing 
fatjjtlicce  adiposcz);  and  sometimes  it  forms  vascular  elevations  resembling 
synovial  villi — the  pleural  villi.  Fat  may  be  found  in  the  pleura  elsewhere. 
The  nerves  of  the  pleura  are  derived  from  the  phrenic,  sympathetic 
and  vagus  nerves.  In  the  parietal  pleura  typical  lamellar  corpuscles  may 
be  found,  together  with  the  smaller  variety,  known  as  the  Golgi-Mazzoni 
corpuscles. 

URINARY  ORGANS. 

WOLFFIAN  BODIES  AND  WOLFFIAN  DlJCTS. 

On  the  twenty-eighth  of  November,  1759,  Caspar  Friedrich  Wolff,  then 
in  his  twenty-sixth  year,  defended  a  thesis  entitled  "Theoria  generations" 
and  obtained  the  degree  of  doctor  of  medicine  at  Halle.  In  addition  to 
the  fundamental  principles  which  this  renowned  thesis  set  forth,  it  included 

an  account  of  the  development  of  the  kidneys  in 
chick  embryos.  From  the  diffuse  substantia 
cellulose,  along  the  ventral  side  of  the  spinal 
column,  beginning  on  the  third  day  of  incuba- 
tion, Wolff  saw  two  elongated  bodies  gradually 
take  form,  and  become  the  kidneys,  each  being 
connected  with  the  cloaca  by  a  ureter.  These 
structures,  however,  are  not  the  kidneys  of  the 
adult,  and  they  are  generally  known  as  Wolffian 
bodies]  their  ureters  are  the  Wolffian  ducts. 
They  are  large  and  important  organs  in  human 
embryos,  as  shown  in  Fig.  302.  The  true  or 
permanent  kidneys  of  mammals  arise  later,  and 
the  Wolffian  bodies  degenerate,  becoming  vesti- 
gial in  the  female;  in  the  male,  however,  they 


i 


al. 


FIG.  302. — DISSECTION  OF  A 
HUMAN  EMBRYO  OF  THIRTY- 
FIVE  DAYS.  (After  Coste.) 

al.,  Bladder;  1.,  lung;  st.,  stom- 
ach; s.  tr.,  septum  trajgfc 
umbili 


cord;  w.  b.,  Wolffian  body;     acquire  new  functions,  and  are  retained  as  a  por- 

W.  d.,  Wolffian  duct.  .  .      .  .      ,      '  ,  ,       , ,          ,  r 

tion  of  the  genital  ducts  (namely  the  duct  of 

the  epididymis).  In  the  embryo  they  are  renal  organs  built  upon  the 
same  plan  as  the  permanent  kidneys,  and  moreover  in  the  fishes  and 
amphibia  they  are  the  kidneys  of  the  adult. 

Still  another  renal  organ  develops  in  embryos,  anterior  to  the  Wolffian 
body,  and  it  has  been  found  that  the  Wolffian  duct  is  primarily  the  duct  of 
this  anterior  kidney  or  pronephros;  consequently  the  Wolffian  duct  is  some-, 
times  called  the  pronephric  duct.  The  pronephros  is  the  functional 
kidney  in  only  the  lowest  of  vertebrates  (myxinoids).  Singularly  it  has 
been  found  that  "  the  human  pronephros  is  by  far  the  best  developed  within 
the  groups  of  mammals "  (Felix,  in  Keibel  and  Mall's  Human  Embry- 


WOLFFIAN  BODIES 


307 


ology,  Vol.  2).  Except  for  its  duct,  it  entirely  disappears  in  very  young 
embryos  (5  mm.).  All  the  renal  organs — pronephros,  Wolffian  body  (or 
mesonephros),  and  kidney  (or  metanephros) — are  developed  from  the 
nephrotomes.  They  are  all  composed  of  mesodermal  tubules,  each  of 
which  is  in  close  relation  with  a  knot  of  capillary  blood  vessels  derived  from 
branches  of  the  aorta.  Such  a  knot  of  vessels  is  a  glomerulus,  and  certain 
products  are  eliminated  from  the  glomerulus  into  the  tubules  to  form  the 
urine. 

Development  of  the  Wolffian  Body  and  Wolffian  Duct.     The  general 
relations  of  the  nephrotome  to  the  mesodermic  somites  and  to  the  ccelomic 


mes.seg". 


Wd. 


FIG.  303. — A,  TRANSVERSE  SECTION  OF  A  RABBIT  EMBRYO  OF  NINE  DAYS;  B,  HUMAN  EMBRYO,  4  MM.; 

C,  HUMAN  EMBRYO,  10  MM. 

ao,  Aorta;  c.,  posterior  cardinal  vein;  coe.,  ccelom;  gl.,  glomerulus;  g.  r.,  genital  ridge;  int.,  intestine;  mes., 
mesentery;  mes.  seg.,  mesodermic  somite;  my.,  myotome;  nch.,  not^|ord;  neph.,  nephrotome ;s-c.v., 
subcardinal  vein;  si.,  sinusoid;  sy.,  sympathetic  nerves;  u.  v.,  umcBtal  vein;  W.  d.,  Wolffian  duct; 
W.  t.,  Wolffian  tubule. 

epithelium  have  already  been  briefly  discussed  (p.  41).  A  nephrotome 
from  a  young  rabbit  embryo  is  seen  in  section  in  Fig.  303,  A,  together  with 
its  elevation  which  contributes  to  the  formation  of  the  Wolffian  duct.  The 
nephrotome  here  shown  is  from  one  of  the  anterior  segments  and  belongs 
with  the  pronephros. 

In  human  embryos,  according  to  Felix,  pronephric  tubules  are  formed 
from  the  seventh  to  the  fourteenth  segments,  and  perhaps  from  those 
further  forward.  The  elevations  to  which  these  nephrotomes  give  rise 
turn  posteriorly  and  unite  with  one  another  to  form  the  Wolffian  duct. 
This  is  at  first  a  solid  cord  of  cells  which  grows  posteriorly  in  the  trough 


308  HISTOLOGY 

between  the  somites  and  somatic  mesoderm.  It  lies  near  the  ectoderm, 
but  it  is  now  generally  agreed  that  the  ectoderm  takes  no  part  in  its  forma- 
tion. Finally  its  growing  extremity  reaches  the  ventral  portion  of  the 
cloaca  and  fuses  with  it.  Later  this  ventral  part  of  the  cloaca  becomes  cut 
off  to  form  the  bladder,  and  the  Wolffian  ducts  then  empty  into  the  neck  of 
the  bladder.  The  pronephric  tubules  meanwhile  become  detached  from 
the  ccelomic  epithelium,  but  they  remain  rudimentary  and  degenerate 
without  having  any  glomeruli  formed  in  connection  with  them. 

The  mesonephric  tubules  develop  from  the  more  posterior  nephrotomes, 
after  the  Wolffian  duct  has  formed.  They  acquire  openings  into  the 
Wolffian  duct,  but  do  not  contribute  to  its  development.  In  produc- 
ing mesonephric  tubules,  the 
nephrotomic  tissue  becomes  de- 
tached and  separates  into  masses 
which  form  vesicles  (Fig.  303,  B). 
Each  vesicle  elongates  and  be- 
comes an  S-shaped  tubule,  one 
end  of  which  fuses  with  the 
Wolffian  duct  and  opens  into  it; 
the  other  end  remains  blind.  A 
knot  of  capillaries,  derived  from  a 

FIG.  304.— RECONSTRUCTION  OF  A  WOLFFIAN  TUBULE      branch    of    the    aorta,    develops    in 

FROM  A  HUMAN  EMBRYO  OF  10.2  MM.     (Except  the        ,         ,.        ,  .  -     ,       0          , 

giomeruius,  after  Koiiman.)  the  distal  concavity  of  the  S  and 

c.,  Inner  layer,  and  c.  a.,  outer  layer  of  the  capsule  of      i  -i  -i  «.lx%-.       ..  ,l,,r 

the  giomeruius;  div.,  diverticulum;  gl.,  giomeruius;      bCCOmCS  a  glOmerUiUS  J  a glOmerUlUS 
W.  d.,  Wolffian  duct.  .      r  j  .  ,  •  • ,  i 

is  formed  in  connection  with  every 

Wolffian  tubule.  The  tubules  then  elongate  and  become  coiled,  and 
together  they  produce  the  rounded  swellings  on  either  side  of  the  root  of 
the  mesentery,  which  are  the  Wolffian  bodies  (Fig.  303,  C).  The  genital 
glands  arise  as  mesodermal  thickenings  on  the  ventro-medial  surface  of 
these  bodies. 

A  single  Wolffian  tubule  is  shown  in  Fig.  304,  and  the  way  in  which  its 
distal  end  envelops  the  giomeruius  is  clearly  indicated.  It  is  said  to  form 
the  capsule  of  the  giomeruius.  By  passing  through  the  inner  layer  of  this 
capsule,  fluid  from  the  blood  vessels  enters  the  tubule  and  is  conveyed 
through  the  Wolffian  duct  to  the  bladder.  The  tubules  are  generally 
unbranched,  and  are  lined  with  simple  epithelium.  The  epithelium  is  in 
part  glandular,  and  contributes  to  the  formation  of  the  urine.  Finally 
it  may  be  noted  that  a  nephrotome  may  divide  into  several  vesicles  (some- 
times perhaps  as  many  as  four),  and  therefore  the  number  of  Wolffian 
tubules  is  greater  than  the  number  of  corresponding  segments.  In  man 
the  maximum  number  is  83  (Felix).  The  mesonephric  tubules  also 
extend  forward,  so  that  some  segments  contain  both  mesonephric  and 
pronephric  tubules. 


ca 


WOLFFIAN  BODIES 


309 


It  is  generally  believed  that  the  Wolffian  bodies  of  mammalian  embryos  are  active 
renal  organs,  producing  a  form  of  urine  which  collects  in  the  allantoic  sac.  In  pig 
embryos  this  sac  and  the  Wolffian  bodies  are  both  unusually  large.  MacCallum  (Amer. 
Journ.  Anat.,  1902,  vol.  i,  pp.  245-259)  notes  that  the  tubules  of  the  Wolffian  body  in 
the  pig  "show  a  very  distinct  division  into  a  secretory  and  a.  conducting  part."  In 
the  human  embryo,  however,  the  allantois  is  very  small  and  the  Wolffian  bodies  de- 
generate early,  before  the  kidney  can  become  functional.  Therefore  Felix  (Keibel  and 
Mall's  Human  Embryology,  vol.  2)  regards  the  question  as  settled.  The  Wolffian 
body  "does  not  function  as  an  excretory  organ";  but  he  adds,  "This  does  not,  of  course, 
imply  that  it  may  not  have  been  active  in  another  manner  unknown  to  us." 

Veins  of  the  Wolffian  Body.  In  determining  the  arrangement  of  the 
large  veins  of  the  abdomen,  the  Wolffian  bodies  are  of  fundamental 
importance.  They  are  supplied  by  the  posterior  cardinal  veins  which 
pass  from  the  tail  of  the  embryo,  on  either  sicje  of  the  aorta,  to  the  heart. 


i  c.  c. 


W.B. 


V.  C.  I. 


il. 


FIG.  305- — THE  TRANSFORMATION  OF  THE  POSTERIOR  CARDINAL  SYSTEM  OF  VEINS. 

c.,  Anterior  cardinal;  as.  1.,  ascending  lumbar;  az.,  azygos;  c.,  caudal;  c.  s.,  coronary  sinus;  h.,  hepatic; 
h.  a.  z.,  hemiazygos;  h.  az.  a.,  accessory  hemiazygos;  il.,  common  iliac;  in.,  innominate;  j.,  jugular; 
K.,  kidney;  1.  c.  c.,  left  common  cardinal;  m.  s.,  median  sacral;  p.  c.,  posterior  cardinal;  r.  c.  c.,  right 
common  cardinal;  s.  c.,  subcardinal;  scl.,  subclavian;  sp.,  spermatic;  sr.,  suprarenal;  sup.,  supracardinal; 
T.,  testis;  v.  c.  i.,  vena  cava  inferior;  v.  c.  s.,  vena  cava  superior;  W.  B.,  Wolffian  body. 

Before  entering  the  right  atrium  of  the  heart,  they  are  joined  by  the 
anterior  cardinal  veins  from  the  head,  thus  forming  the  right  and  left 
common  cardinal  veins,  or  "ducts  of  Cuvier."  As  each  posterior  cardinal 
vein  extends  along  the  dorsal  side  of  the  Wolffian  body,  it  sends  branches 
in  among  the  tubules,  and  these  unite  ventrally  on  either  side  in  the 
subcardinal  vein  (Fig.  305,  A).  Thus  each  Wolffian  body  is  lodged  in  a 
venous  loop  formed  by  the  posterior  cardinal  and  subcardinal  veins,  and 


310  HISTOLOGY 

such  a  loop  is  found  in  all  classes  of  vertebrates.  Venous  blood  entering 
the  Wolffian  body  posteriorly  flows  out  from  it  anteriorly,  and  circulates 
among  the  tubules  in  lacunar  vessels,  closely  resembling  the  hepatic  sinu- 
soids. This  is  the  " renal  portal  system."  It  should  be  noted,  however, 
that  the  renal  sinusoidal  vessels  are  poorly  developed  in  mammalian 
embryos. 

In  sections  these  veins  are  readily  recognized.  The  mesonephric 
arteries  pass  from  the  aorta  to  the  glomeruli  of  the  Wolffian  body,  between 
the  subcardinal  vein  in  front  and  posterior  cardinal  vein  behind  (Fig. 
303,  C).  In  places,  the  subcardinal  veins  form  large  anastomoses  across 
the  mid-ventral  line;  the  posterior  cardinal  veins  are  further  apart,  and 
receive  intersegmental  branches  from  the  dorsal  musculature. 

As  the  kidneys  grow  upward  behind  the  Wolffian  bodies,  their  ureters 
become  encircled  by  a  branch  from  the  posterior  cardinal  vein  (Fig.  305, 
A).  The  venous  loop  around  the  ureter  was  described  by  Hochstetter 
(Morph.  Jahrb.,  1893,  vol.  20,  pp.  543-648),  and  its  dorsal  limb,  together 
with  secondary  anastomoses,  has  been  named  the  supracardinal  vein 
(Huntington  and  McClure,  Anat.  Rec.,  1907,  vol.  i,  pp.  29-30).  The 
transformation  of  these  veins  into  the  branches  of  the  inferior  vena  cava 
is  represented  somewhat  diagrammatically  in  Fig.  305,  B,  and  may  be 
briefly  described  as  follows: 

The  anastomosis  between  the  subcardinal  veins  becomes  a  part  of  the  left  renal 
vein.  Above  this  anastomosis  the  right  subcardinal  vein  connects  with  the  veins  of  the 
liver  and  forms  a  portion  of  the  vena  cava  inferior.  The  left  subcardinal  vein,  above 
the  renal  anastomosis,  becomes  reduced  to  the  left  suprarenal  vein  (Hochstetter).  The 
subcardinal  veins  below  the  renal  anastomosis  are  associated  with  lymphatic  vessels  to 
which  they  apparently  give  rise;  otherwise  they  disappear. 

The  posterior  cardinal  veins  above  the  renal  anastomosis,  after  they  have  been 
tapped  by  the  formation  of  the  vena  cava  inferior,  are  known  as  the  azygos  and  hemi- 
azgos  veins,  and  the  outlet  of  the  left  common  cardinal  becomes  cut  off  as  the  coronary 
sinus  (Fig.  305,  B,  which  shows  also  the  formation  of  the  superior  vena  cava).  Below 
the  renal  anastomosis  the  posterior  cardinal  veins  give  rise  to  the  genital  veins  (sper- 
matic or  ovarian),  and  the  Wolffian  body  becomes  reduced  to  an  appendage  of  the  geni- 
tal glands.  As  the  genital  glands  descend  into  the  pelvis,  their  veins  become  elongated; 
and  the  corresponding  arteries,  derived  from  the  mesonephric  arteries,  are  likewise 
elongated.  The  supracardinal  vein  on  the  right  side  becomes  a  part  of  the  vena  cava 
inferior;  on  the  left  it  is  probably  represented  by  the  ascending  lumbar  vein. 

The  kidneys  are  supplied  by  vessels  which  enter  them  after  they  have  attained  their 
permanent  position.  Their  arteries  and  veins  consequently  pursue  a  straight  course 
from  the  aorta  and  vena  cava,  respectively,  to  the  hilus  of  the  kidney. 

KIDNEY. 

Development.  The  kidney  develops  after  the  Wolffian  body  has  been 
formed.  It  arises  in  two  parts,  one  of  which  is  an  outgrowth  of  the  Wolf- 
fian duct;  the  other  is  a  mass  of  dense  mesenchyma  surrounding  this 
outgrowth,  and  said  to  be  derived  from  the  posterior  nephrotomes.  Both 


KIDNEY 


parts  are  mesodermal.     The  part  derived  from  the  Wolffian  duct  may  be 
considered  first. 

Each  Wolffian  duct,  near  the  place  where  it  enters  the  cloaca,  forms  a 
knob-like  outpocketing  which  elongates  rapidly,  becoming  the  ureter. 
The  distal  end  of  the  outpocketing  expands  and  becomes  lobular,  thus 
producing  the  pelvis  of  the  kidney.  After  the  ventral  part  of  the  cloaca 


Wd.     Md. 


,ald. 


cJ. 


FIG.  306. — THE  DEVELOPMENT  OF  THE  RENAL  PELVIS  AND  URETER.     (Keibel.) 

A,  Human  embiyo  of  11.5  mm.  (4$  weeks);  B,  25  mm.  (8$-p  weeks),  a.,  Anus;  al.  d.,  allantoic.  duct 
bl.,  bladder;  cl.,  cloaca;  M.  d.,  Mullerian  duct;  p.,  pelvis  of  the  kidney;  r.,  rectum;  ur.,  ureter;  u.  s., 
urogenital  sinus;  W.  d.  Wolffiian  duct. 

has  been  split  off  to  form  the  bladder,  the  ureter  and  Wolffian  duct,  on 
either  side,  open  into  it  by  a  common  outlet  (Fig.  306,  A).  Later,  the 
terminal  portion  of  each  Wolffian  duct  is  taken  up  into  the  wall  of  the 
expanding  bladder,  so  that  the  ureters  acquire  openings  separate  from 


PIG.  307. — RECONSTRUC- 
TION OF  THE  URETER, 
RENAL  PELVIS,  AND 
ITS  BRANCHES  IN  A  20- 
MM.  HUMAN  EMBRYO. 
(Huber.) 


FIG.  308. — FROM  A  SECTION  OF  A  KIDNEY  OF  AN  18- 
MM.  HUMAN  EMBRYO.  X  233.  (Huber.) 

a.,  Primary  collecting  tubule,  with  dilated  extremity; 
b,b'.,  inner  layer,  and  c.,  outer  layer  of  dense  mes- 
enchyma;  d.,  loose  mesenchyma;  e.,  vesicle,  the 
beginning  of  a  renal  tubule. 


those  of  the  ducts.     With  further  growth  the.  orifices  of  the  Wolffian  ducts 
are  carried  toward  the  median  line  and  downward  toward  the  outlet  of 
the  bladder  (Fig.  306,  B),  and  this  position  is  permanently  retained. 
Meanwhile  the  lobes  of  the  renal  pelvis  have  become  deeper  and  formed 


312 


HISTOLOGY 


pouches  known  as  the  major  and  minor  calyces.  In  the  adult  there  are 
usually  two  major  calyces,  one  at  either  end  of  the  pelvis,  and  from  these 
most  of  the  minor  calyces  grow  out;  the  others  spring  directly  from  the 
main  pelvic  cavity.  There  are  about  eight  in  all.  From  the  minor  caly- 
ces the  collecting  tubules  grow  out.  Each  tubule  has  an  enlarged  extremity 


FIG.  309. — MODELS  SHOWING  SUCCESSIVE  STAGES  IN    THE    DEVELOPMENT  OF  A  URINIFEROUS  TUBULE 

INCLUDING  THE  ASSOCIATED  PORTION  OF  THE  COLLECTING  TUBULE.     (Huber.) 

From  a  human  embryo  of  the  seventh  month.     X  160. 

(Fig.  307)  which  divides  into  two  branches  with  a  U-shaped  crotch,  like 
a  tuning-fork.  The  branches  subdivide  repeatedly  in  the  same  manner, 
so  as  to  make  pyramidal  masses  of  straight  tubules  radiating  from  the 
calyces.  Thus  the  renal  outgrowth  from  the  Wolffian  duct  produces  the 


KIDNEY 


313 


epithelial  lining  of  the  ureter,  pelvis,  calyces  and  collecting  tubules,  includ- 
ing all  of  their  branches. 

The  second  part  of  the  kidney,  which  consists  of  dense  mesenchyma, 
becomes  subdivided  into  masses  enveloping  the  enlarged  tips  of  the  branch- 
ing collecting  tubules.  Some  of  its  cells 
become  arranged  so  as  to  form  vesicles 
(Fig.  308),  one  of  which  is  shown  in  the 
reconstruction,  Fig  309,  A.  The  vesi- 
cles are  at  first  entirely  separate  from 
the  collecting  tubules.  Each  vesicle 
becomes  elongated,  making  an  S-shaped 
tubule  (Fig.  309,  B,  C),  and  its  outer 
or  upper  end  unites  with  the  collecting 
tubule  (Fig.  309,  D).  A  glomerulus 
develops  in  the  lower  curve  of  the  S, 
and  is  gradually  enveloped  in  the 
terminal  part  of  the  tubule,  which  thus 
forms  its  capsule.  Between  the  cap- 
sule and  the  collecting  tubule,  the  renal 
tubules  become  greatly  convoluted. 
One  of  the  loops  in  the  coils  thus  formed 
elongates  downward,  lying  close  beside 
and  parallel  with  the  collecting  tubule; 
this  is  the  loop  of  Henle  (Fig.  309,  J). 

Three  tubules  of  the  adult  kidney 
are  shown  diagrammatically  in  Fig.  310. 
Each  capsule  connects  with  a  proximal 
convoluted  tubule,  which,  after  extending 
outward  toward  the  surface  of  the  kid- 
ney, turns  downward  as  the  descending 
limb  of  Henle's  loop.  The  descending 
limb  is  a  straight  tubule,  the  lower  por- 
tion of  which  is  of  small  diameter  owing 
to  the  flatness  of  the  cells  in  its  walls; 
its  lumen  is  not  reduced.  This  "thin 
segment/'  as  shown  in  the  diagram, 
does  not  form  the  entire  descending 

limb,  but  only  its  lower  part.  Frequently  it  passes  around  the  bend  into 
the  ascending  limb.  The  tubule,  after  turning  the  bend,  forms  the  ascend- 
ing limb  of  Henle's  loop.  It  returns  to  the  vicinity  of  the  capsule  from 
which  it  arose,  and  makes  a  few  coils,  thus  constituting  the  distal  convo- 
luted tubule  (intercalated  or  intermediate  tubule).  By  means  of  the 
functional  tubule  it  joins  the  arched  collecting  tubule  and  this  passes  into 


D. 


FIG.  310. — DIAGRAM  OF  THREE  URINIFEROUS 
TUBULES  IN  RELATION  WITH  A  COLLECT- 
ING TUBULE.  (Modified  from  Huber.) 

a.  1.,  Ascending  limb  of  Henle's  loop;  c.,  cap- 
sule; c.  t.,  collecting  tubule;  d.  c.,  distal 
convoluted  tubule;  d.  1.,  descending  limb; 
j,,  junctional  tubule;  p.  c.,  proximal  con- 
voluted tubule;  p.  d.,papillary  duct. 

A,  cortex;  B-D,  medulla,  subdivided  into  an 
inner  zone  (D)  and  an  outer  zone  (B-C) ; 
the  latter  includes  an  inner  band  or  stripe 
(C),  and  an  outer  band  (B). 


3*4 


HISTOLOGY 


the  straight  descending  collecting  tubule.  From  the  capsule  to  the  collect- 
ing tubule  no  branches  occur;  and  this  extent  of  the  tubule  represents  the 
part  derived  from  mesenchyma.  The  collecting  tubules  receive  many 
branches.  Traced  toward  their  outlet  in  the  pelvis  they  become  larger, 
finally  forming  the  papillary  ducts. 

In  the  diagram  (Fig.  310)  the  tubules  are  represented  as  much  coarser  than  is  actu- 
ally the  case.  Their  true  proportions  in  the  rabbit's  kidney  have  been  shown  by  Huber, 
who,  with  extraordinary  success,  has  isolated  individual  tubules,  keeping  them  intact 
from  the  capsule  to  the  collecting  tubule  (Anat.  Rec.,  1911,  vol.  5,  pp.  187-194).  They 
are  20-30  mm.  in  length  and  less  than  o.i  mm.  in  diameter.  Huber's  account  of  the 
development  of  the  kidney,  from  which  Figs.  307-309  have  been  taken,  is  in  the  supple- 
ment to  the  Amer.  Journ.  Anat.,  1905,  vol.  4. 

Surface  Markings.  Before  studying  sections  of  the  kidney  micro- 
scopically, the  small  subdivisions  of  the  organ  which  may  be  seen  upon  its 
cut  surface  should  be  examined.  They  are  shown  in  transverse  section 
in  Fig.  311,  but  appear  equally  well  when  the  kidney  is  divided  length- 


Cortex. 

Pars  convoluta.  Pars  radiata. 


Pelvis. 

Renal  artery. 
Ureter. 

Renal  vein. 
Calyx. 


Pyramid 

(Medulla). 

Papilla. 


Renal  column. 


FIG.  311. — THE  SURFACE  MARKINGS  OF  THE  HUMAN  KIDNEY.     (After  Brodel.) 


wise.  The  ureter  opens  into  the  pelvis,  which  is  prolonged  into  the  cup- 
like  calyces,  two  of  which  are  shown  in  Fig.  311.  Each  calyx  receives 
a  nipple-like  projection  of  the  substance  of  the  kidney,  known  as  a  renal 
papilla.  Sometimes  two  of  them  project  into  one  calyx.  They  are  soft, 
dark  red  structures,  and  it  does  not  appear  on  inspection  that  the  grayish 
lining  of  the  calyx  is  reflected  over  their  outer  surface;  this  is  seen  in  sec- 
tions. Toward  the  apex  of  each  papilla  there  are  from  15  to  20  foramina, 
which  are  the  orifices  of  as  many  papillary  ducts;  through  them  the  urine 
enters  the  calyx.  The  foramina  are  barely  visible  without  magnifica- 
tion. Each  papilla  forms  the  apex  of  a  renal  (or  Malpighian)  pyramid, 
described  by  Malpighi  (1666)  in  his  treatise  "  on  the  structure  of  the  vis- 
cera," which  gave  the  first  account  of  various  almost  microscopic  "corpus- 


KIDNEY  315 

cles"  and  surface  markings.  The  base  of  the  pyramid  is  toward  the 
periphery  of  the  kidney,  and  may  be  lobular  as  in  the  figure.  From  two 
to  nine  embryonic  or  primary  pyramids  are  said  to  fuse  to  form  a  pyramid 
of  the  adult  kidney.  In  favorable  specimens  the  pyramid  is  seen  to  be 
divided  into  an  inner  and  an  outer  zone,  and  the  latter  is  composed  of  two 
concentric  bands.  The  significance  of  these  markings  will  be  considered 
later.  The  pyramids  collectively  constitute  the  medulla  of  the  kidney, 
a  term  more  fittingly  applied  to  the  kidneys  of  many  animals  which  have 
but  a  single  pyramid.  The  base  of  each  pyramid  is  surrounded  by  a 
lighter  zone,  the  cortex,  which  shows  radial  striations.  With  low  magnifi- 
cation the  striations  are  seen  to  taper  outward.  They  constitute  the 
processes  or  pyramids  of  Ferrein  and  are  known  collectively  as  the  radiate 
part  of  the  cortex  (pars  radiata).  They  consist  of  straight  radial  tubules 
which  are  continuous  with  those  in  the  medulla.  Consequently  they  are 
often  called  "  medullary  rays,"  but  being  in  the  cortex  they  may  more 
properly  be  designated  "  cortical  rays."  Between  these  rays  is  the  con- 
voluted part  of  the  cortex  (pars  convoluta);  it  may  be  recognized  by  the 
presence  of  many  renal  corpuscles  (Malpighian  corpuscles),  which  are 
bodies  consisting  of  a  glomerulus  and  its  surrounding  capsule.  They  are 
barely  visible  without  magnification. 

Over  the  outer  surface  of  the  kidney,  there  is  a  fibrous  capsule  (tunica 
fibrosa)  which  may  be  readily  stripped  off  when  normal;  and  outside  of 
this  there  is  a  fatty  layer  (capsula  adiposd).  The  fat  surrounds  the  pelvis 
and  extends  into  a  hollow  of  the  kidney  known  as  the  renal  sinus;  this  is 
the  excavation  which  contains  the  pelvis  and  its  calyces.  In  this  fatty 
tissue  the  large  blood  vessels  enter  the  kidney,  passing  chiefly  over  the 
anterior  or  ventral  surface  of  the  pelvis;  having  reached  the  boundary 
zone  between  cortex  and  medulla  they  enter  it,  and  pursue  an  arched 
course,  giving  off  both  cortical  and  medullary  branches.  In  certain  places, 
the  cortex  dips  down  to  the  renal  sinus;  this  occurs  between  the  Mal- 
pighian pyramids,  and  constitutes  the  renal  columns  (of  Bertini);  one  of 
them  is  shown  in  Fig.  311. 

The  arrangement  of  the  renal  tubules  in  relation  to  the  cortex  and 
medulla  is  as  follows.  The  convoluted  part  of  the  cortex  contains  the 
capsules,  and  both  proximal  and  distal  convoluted  tubules.  The  rays 
contain  the  collecting  tubules,  together  with  the  outer  portions  of  Henle's 
loops.  The  medulla  contains  the  larger  collecting  tubules  and  the  deeper 
portions  of  Henle's  loops;  since  these  are  all  straight  tubules,  the  medulla 
resembles  the  radiate  part  of  the  cortex.  Tubules  which  are  connected 
with  capsules  deep  in  the  cortex,  near  the  boundary  zone,  send  their 
Henle's  loops  much  further  into  the  medulla  than  those  from  the  outer 
capsules;  and  in  the  deeply  placed  tubules  the  thin  segment  of  Henle's 
loop  is  not  limited  to  the  descending  limb  but  extends  well  up  into  the 


HISTOLOGY 


ascending  limb.  Thus  it  happens  that  a  broad  inner  zone  of  the  medulla 
(i.e.,  toward  the  papilla)  contains  only  thin  segments  of  renal  tubules 
in  addition  to  the  large  collecting  tubules  (Fig.  310,  D);  and  the  zone 
so  characterized  may  be  distinguished  macroscopically.  The  papilla  con- 
tains only  collecting  tubules,  but  the  loops  of  Henle  turn  back  at  different 
levels,  and  therefore  the  papillary  zone  entirely  free  from  loops  is  not  well 
denned.  The  outer  zone  of  the  medulla  contains  both  thick  and  thin  seg- 

Renal  corpuscle.        Convoluted  tubules.        Cortical  ray. 


Interlobular  vein. 


Henle's  loop.  Arciform  vein.       Arciform   artery. 

FIG.  312. — PART  OF  A  RADIAL  SECTION  OF  A  HUMAN  KIDNEY.     X  25. 
At  x  a  renal  corpuscle  has  dropped  out. 

ments  of  Henle's  loops,  in  addition  to  the  collecting  tubules.  In  the  de- 
scending limbs  the  change  to  thin  segments  occurs  at  a  more  or  less  definite 
level  within  this  outer  zone,  thus  subdividing  it  into  a  narrow  outer  band, 
with  few  thin  segments,  and  an  inner  band  containing  many  of  both  sorts. 
These  zones  have  only  recently  been  recognized  (Peter,  Untersuchungen 
iiber  Bau  und  Entwickelung  der  Niere,  Jena,  1909). 

The  renal  tubules  which  have  their  capsules  close  to  the  medulla  are 
the  first  to  develop ;  the  others  are  formed  successively  outward,  the  young- 


KIDNEY 


317 


est  being  immediately  beneath  the  capsule.  Thus  a  single  section  of  an 
embryonic  kidney  shows  various  stages  in  the  development  of  the  tubules. 
Sections  of  the  Kidney.  Since  a  radial  section  of  the  kidney  shows  both 
cortex  and  medulla,  it  is  the  form  usually  made  for  pathological  examina- 
tions (Fig.  312).  The  tubules  may  be  studied  to  better  advantage, 
however,  in  tangential  sections,  one  through  the  cortex  and  the  other 
through  the  medulla.  The  tubules  are  then  seen  in  cross  section.  The 

Capsule  of  the  *%  T 

glomerulus 
(outer  layer.)        JS 


•^-c^-w- j  \ 
>l 

B    l^rv 


Thick  segment  of 
the  descending 
limb  of  Henle's 
loop. 


Proximal  convoluted 
tubule. 


Capillary. 
Ascending  limb  of  Henles*  loop.  ; 

Collecting  tubule. 

FIG.  313. — TANGENTIAL  SECTION  OF  THE  CORTEX  OF  A  HUMAN  KIDNEY.     X  200.     (Schaper.) 
The  pars  radiata  is  seen  in  the  lower  left  corner.     The  line  from  "capsule  of  the  glomerulus "  passes  between 

two  distal  convoluted  tubules. 


rays  of  the  cortex  appear  as  islands  of  circular  sections  surrounded  by  the 
irregular  convoluted  tubules,  among  which  are  the  scattered  renal  cor- 
puscles. The  greater  part  of  such  an  island  is  shown  in  the  lower  portion 
of  Fig.  313,  The  renal  tubules  are  lined  throughout  with  simple  epithelium 
and  their  characteristic  features  will  now  be  considered,  beginning  with 
the  glomerular  capsule. 

The  glomerular  capsule  (of  Bowman)  consists  of  two  layers.     Its  inner 


HISTOLOGY 


layer  is  a  flat  syncytium  blending  with  the  perivascular  tissue'  of  the 
glomerulus,  and  following  its  lob  illations.  The  outer  layer  of  the  capsule 
is  smooth,  and  is  composed  of  flat  polygonal  cells.  Terminal  bars,  which 
have  been  found  in  all  other  divisions  of  the  renal  tubules,  have  not 
been  demonstrated  in  the  capsule.  The  flat  epithelium  of  the  outer  layer 
changes  at  the  "neck"  of  the  capsule  to  the  low  columnar  epithelium 
of  the  proximal  convoluted  tubule.  The  neck  may  occur  in  various 
positions,  generally  being  opposite  the  aperture  through  which  the  vessels 
enter  and  leave.  The  space  between  the  layers  of  the  capsule  is  continuous 
with  the  lumen  of  the  convoluted  tubule. 

The  proximal  convoluted  tubules  are  large  (40-60 /*  in  diameter) ,  with 
irregular  lumens  and  indistinct  cell  walls.  In  some  animals  the  walls 
are  folded  so  as  to  be  vertically  plaited.  The  cells  show  signs  of  secretory 
activity  and  are  believed  to  excrete  urea  and  pigments;  the  fluid  part  of 
the  urine  comes  chiefly  from  the  glomeruli.  The  nuclei  are  toward  the  base 


FIG.  314- — CROSS  SECTION  OF  A  CON- 
VOLUTED TUBULE  FROM  A  RABBIT. 
(Szymonowicz.) 


FIG.  '315. — TUBULES  OF  THE  PARS  RADIATA.     FROM  A  RADIAL 
SECTION  OF  A  HUMAN  KIDNEY.     X  240. 


of  the  cells,  and  the  protoplasm  contains  granules  arranged  in  vertical 
rows  which  form  basal  rods  (Fig.  314).  Toward  the  lumen  there  is  a 
"brush  border"  suggestive  of  short  non-motile  cilia.  It  is  uncertain 
whether  this  is  normal  or  due  to  post-mortem  disintegration.  Clear 
spaces  are  sometimes  seen  in  the  outer  part  of  the  cells.  The  lumen  is 
wide  and  the  cells  are  low  after  copious  urine  production;  and  the  reverse 
is  true  when  the  urine  is  scanty. 

The  upper  segment  of  the  descending  limb  of  Henle's  loop  is  similar 
in  structure  to  the  proximal  convoluted  tubules.  It  is  a  straight  tubule, 
however,  and  is  found  in  the  radiate  part  of  the  cortex  (Fig.  313). 

The  upper  segments  of  the  ascending  limbs  are  also  found  in  the  pars 
radiata.  Their  protoplasm  is  less  granular  than  that  of  the  descending 
limbs,  but  closely  resembles  that  of  the  distal  convoluted  tubules.  The 
latter  are  typically  shown  in  Fig.  313  (there  being  one  on  either  side  of  the 
label  line  to  the  "capsule  of  the  glomerulus").  Huber  (loc.  cit.)  describes 
these  tubules  as  showing  "an  outer  dark  zone  which  is  finely  striated, 


KIDNEY  319 

and  an  inner  zone  which  is  lighter,  the  nuclei  being  placed  at  the  junction 
of  the  two  zones."  It  is  probable,  from  their  position,  that  the  distal 
convoluted  tubules  in  Fig.  313  are  parts  of  the  tubule  which  connects 
with  the  glomerulus  shown  in  the  figure. 

The  arched  collecting  tubules,  into  which  the  distal  convoluted  tubules 
empty,  pass  into  the  collecting  tubules  of  the  rays,  which  are  readily 
identified.  They  have  round  and  clear-cut  lumens;  cell  walls  are  distinct 
(in  all  but  the  smallest),  and  the  nuclei  are  regularly  arranged.  Thus 
the  collecting  tubule  resembles  an  excretory  duct. 

The  structures  seen  in  the  radiate  part  of  the  cortex  are  therefore  the 
ascending  and  descending  limbs  of  Henle's  loops,  and  the  collecting  tubules; 


Large  collecting  tubule. 


Thick  segments 

-*  Henle's  loop 

(ascending). 

Capillary.  ^y§^y^^'-        &  ^  ',     'V€'"---jt^^        Thin  segments 

f  Henle's  loop 
(descending) . 


m 

FIG.  316. — TRANSVERSE  SECTION  THROUGH  THE  MEDULLA  OF  A  HUMAN  KIDNEY.     X  320.      (Schaper.) 

they  are  shown  in  longitudinal  section  in  Fig.  315.  The  convoluted  part 
of  the  cortex  contains  proximal  and  distal  convoluted  tubules  and  glomeru- 
lar  capsules. 

The  medulla  (Fig.  316)  contains  the  same  elements  as  the  rays.  The 
collecting  tubules  are  larger,  and  their  walls  are  more  distinct.  Among 
their  columnar  cells  a  few  are  decidedly  darker  than  the  others.  The  thick 
segments  of  Henle's  loops  are  easily  distinguished  from  the  thin  segments. 
The  latter  are  slender  (9-16  A*  in  diameter)  but  have  large  lumens.  Cell 
walls  are  absent,  and  the  cells  are  so  flat  that  their  nuclei  cause  elevations. 
The  thin  segments  are  generally  descending,  but  they  may  also  ascend,  as 
seen  in  the  inner  zone  of  the  medulla ;  Fig.  3 1 5  is  from  the  outer  zone,  in  which 
most,  if  not  all,  of  the  thin  segments  are  descending.  (In  comparing 
Fig.  316  with  Fig.  313,  it  should  be  noted  that  the  former  is  more  highly 
magnified,  and  the  thick  ascending  limbs  appear  more  granular  than  those 
tubules  of  the  cortex  with  which  they  are  continuous.) 


320 


HISTOLOGY 


Connective  tissue.  Between  the  renal  tubules  there  is  a  small  amount 
of  interstitial  connective  tissue.  It  is  more  abundant  toward  the  papillae 
and  around  the  vessels  and  glomeruli  than  elsewhere.  Beneath  the 


Arched    col- 
ecting  tubule. 


Papillary  duct.- 


Lobule. 


Lobule. 


--   Tunica  fibrosa. 


Stellate  vein. 


Interlobular 

artery. 

Interlobular 

vein. 


.,  Arcif  orm  artery 


Arcif  orm  vein. 


Interlobar  artery. 

Interlobar  vein. 


FIG.  317. — DIAGRAM  OF  THE  COURSE  OF  THE  RENAL  BLOOD  VESSELS. 

epithelium  of  the  tubules  it  forms  basement  membranes,  apparently 
homogeneous,  but  actually  composed  of  fine  fibrils.  The  normal  amount 
of  interstitial  tissue  should  be  carefully  studied,  since  its  increase  is  indica- 
tive of  an  important  pathological  condition.  This  tissue  is  continuous 


KIDNEY 


321 


with  that  of  the  fibrous  capsule.     The  latter  contains  elastic  fibers,  which 
increase  in  abundance  with  age,  and  also  smooth  muscle  fibers. 

Lobes  and  lobules.  In  embryonic  life  the  kidney  is  divided  into  lobes, 
bounded  by  the  renal  columns,  and  indicated  by  grooves 
upon  the  outer  surface  (Fig.  318).  The  grooves  become 
obliterated  during  the  first  year.  In  the  ox  similar 
grooves  are  permanent;  in  many  mammals  as  in  the  cat 
and  rabbit,  they  never  exist,  since  the  kidney  has  but 
one  lobe,  papilla  and  pyramid.  The  lobules  or  structural 
units  of  the  kidney  are  the  areas  centering  around  each 
radiate  division  of  the  cortex,  by  which  they  are  drained 

/_,.  x         ~,  ill  •  FlG-  3i8. — KIDNEY  OF 

(Fig.  317).     They  are  not  bounded  by  connective  tissue       A  CHILD  AT  BIRTH. 

( After  Hertwig.) 

septa. 

Blood  vessels.  The  kidney  has  a  capillary  circulation.  The  renal 
artery  passes  from  the  aorta  to  the  hilus,  or  notch  on.  the  medial  border  of 
the  kidney.  It  divides  into  several  branches,  most  of  which  pass  over  the 


Elongated 

capillary 

meshes. 


Round 
capillary 
meshes. 

V-j/.  "L  Partly  injected  glomeruli. 

Tnterlobular  artery. 
"~~  Interlobular  vein. 
FIG.  319. — FROM  A  SECTION  OF  THE  INJECTED  CORTEX  OF  AN  ADULT  HUMAN  KIDNEY.    X  30. 

ventral  surface  of  the  pelvis  into  the  fat  around  the  calyces  (Fig.  311). 
Thence,  as  interlobar  arteries,  they  extend  to  the  boundary  layer  between 
the  cortex  and  medulla  where  they  are  known  as  arciform  arteries  (Fig. 
317).  These  send  interlobular  arteries  through  the  convoluted  part  of  the 
cortex  and  their  terminal  branches  enter  the  fibrous  capsule.  It  will  be 
noted  tha't  the  kidney  is  exceptional  in  having  its  arteries  at  the  periphery 
of  its  lobules.  From  the  interlobular  arteries  small  stems  pass  to  the  glo- 
meruli, each  of  which  receives  a  single  twig  (Fig.  319).  This  is  resolved  into 
a  knot  of  capillary  loops,  the  endothelium  of  which  seems  to  blend  with  the 
surrounding  syncytium  and  indirectly  with  the  inner  layer  of  the  capsule. 


322  HISTOLOGY 

The  glomerulus  often  appears  lobed,  due  to  the  arrangement  of  its  vascular 
loops.  The  capillaries  unite  to  form  a  single  efferent  vessel  which  is  smaller 
in  diameter  than  the  afferent  vessel;  thus  the  pressure  within  the  glomeru- 
lus is  increased.  The  entire  glomerulus  is  regarded  as  arterial.  On  leav- 
ing it,  the  efferent  vessel  divides  into  small  branches.  These  spread 
among  the  convoluted  and  straight  tubules  of  the  cortex,  and  some  con- 
tinue into  the  medulla.  The  latter  is  supplied  also  by  straight  branches  (ar- 
teriola  recta)  from  the  interlobular,  efferent  and  arcif orm  arteries,  as  shown 

in  Fig.  317.  The  veins  of  the  medulla  begin 
around  the  papillae,  and  as  venula  recta  empty 
into  the  arciform  veins.  The  cortical  veins  are 
the  interlobular  vessels  which  are  beside  the 
corresponding  arteries.  They  arise  from  con- 
verging veins  in  the  renal  capsule,  which  on 
surface  view  form  stellate  figures  (vena 
stellata).  The  interlobular  veins  drain  the 
capillaries  of  the  cortex,  but  have  no  direct 
relation  with  the  glomeruli.  Interlobar  veins 
follow  the  arteries,  passing  out  from  the  hilus  of 
.  .  *  ^  the  kidney  over  the  ventral  surface  of  the  renal 

Urmiferous  tubules. 
FIG.  320. — FROM  THE  KIDNEY  OF  A     Peiv  s> 

MOTOR.    GOLGI  PREPARATION.          Lymphatic  vessels  are  said  to  occur  within 

the  cortex  and  to  follow  the  blood  vessels  out  at 

the  hilus.  The  cortical  lymphatics  also  pass  through  the  tunica  fibrosa 
to  connect  with  a  network  in  the  adipose  capsule.  They  proceed  to 
neighboring  lymph  glands. 

The  nerves  are  medullated  and  non-medullated.  There  is  a  sym- 
pathetic plexus  at  the  hilus  associated  with  small  ganglia,  and  from  it 
interlacing  nerves  extend  into  the  kidney  around  the  vessels  (Fig.  320). 
Fine  branches  supply  the  epithelial  cells,  especially  those  of  the  convoluted 
tubules.  They  form  plexuses  beneath  and  above  the  basement  membrane, 
and  have  free  intercellular  endings. 

RENAL  PELVIS  AND  URETER. 

The  renal  pelvis  and  ureter  both  consist  of  a  mucosa  (and  submucosa), 
muscularis  and  adventitia  (Fig.  321.)  The  mucosa  includes  the  epithelium 
and  tunica  propria,  the  latter  blending  with  the  submucosa.  In  sections 
the  epithelium  resembles  that  of  the  moderately  contracted  bladder  (Fig. 
322),  and  its  cells  when  found  detached  in  urine  are  not  distinguishable 
from  bladder  cells.  The  epithelium  is  stratified  but  consists  of  few  layers. 
The  basal  cells  are  rounded,  those  of  the  middle  layer  are  club  shaped  or 
conical  with  rounded  ends,  and  the  outer  cells  are  columnar,  cuboidal, 


URETER 


323 


or  somewhat  flattened.  Their  lower  surface  may  be  indented  by  the  rounded 
ends  of  several  underlying  cells,  as  is  particularly  the  case  in  the  contracted 
bladder  (Fig.  323).  Two  nuclei  are  often  found  in  a  superficial  cell,  and 


Tunica  adventitia. 


Tunica 
muscularis. 


(Submucosa.) 


FIG.  321. — TRANSVERSE  SECTION  OF  THE  LOWER  HALF  OF  A  HUMAN  URETER.     X  15. 

c.,  Epithelium;  t.,  tunica  propria;  1,  inner  longitudinal  muscle  bundles;  r,  circular  layer  of  muscle  bundles; 

li,  outer  longitudinal  muscle  bundles. 

in  some  animals  they  are  known  to  arise  by  amitosis.  Leucocytes  fre- 
quently enter  the  epithelium.  In  some  animals  mucous  glands  have 
been  found  extending  into  the  tunica  propria,  and  there  are  gland-like 
pockets  in  man.  Some  of  these  have  no  lumen  and  it  is  said  that  none 


FIG.  322. — VERTICAL  SECTION  OF  THE  Mucous  MEMBRANE  OF    A 

HUMAN  BLADDER.     X  560. 

a,  Columnar  cell  with  cuticular  border;  b,  lymphocyte;  c,  tunica 
propria. 


FIG.  323-— A  SUPER- 
FICIAL EPITHELIAL 
CELL  AND  Two 
CLUB-SHAPED 
CELLS  FROM  A  CON- 
TRACTED BLADDER. 
(KoeUiker.) 


are  true  glands.  Capillary  blood  vessels,  which  are  abundant  in  the 
mucosa,  are  found  directly  beneath  the  epithelium  and  present  the  decep- 
tive appearance  of  becoming  intra-epithelial.  The  tunica  propria  consists  of 
fine  connective  or  reticular  tissue,  with  few  elastic  fibers.  It  contains 


324 


HISTOLOGY 


many  cellular  elements  and  some  lymphocytes,  and  passes  without  a 
definite  boundary  into  the  loose  connective  tissue  of  the  submucosa. 

The  tunica  muscularis  has  considerable  connective  tissue  among  its 
smooth  muscle  bundles.  The  latter  form  an  inner  longitudinal  and  an 
outer  circular  layer.  In  the  lower  half  of  the  ureter  there  is  a  third,  outer 
longitudinal  layer,  specially  thickened  along  the  last  5  cm.  Around  the 
papillae  of  the  kidney  the  circular  fibers  form  a  "  sphincter/'  The  part 
of  the  ureter  which  passes  obliquely  through  the  wall  of  the  bladder  has 
only  longitudinal  fibers,  ending  in  the  tunica  propria  of  the  bladder.  By 
contracting  they  open  the  outlet  of  the  ureter.  The  adventitia  consists 
of  loose  fibro-elastic  connective  tissue. 

Lymphatics  and  blood  vessels  are  numerous.  There  are  sympathetic 
nerves  to  the  muscles,  and  free  sensory  endings  in  the  tunica  propria 
and  epithelium. 

BLADDER. 

The  development  of  the  bladder  from  the  ventral  part  of  the  cloaca 
has  been  described  on  page  245.  Its  epithelium  is  entodermal  whereas 
that  of  the  ureters  opening  into  it  is  mesodermal.  There  is  however  no 
demarcation  between  the  layers  in  the  adult,  since  both  produce  the  same 
sort  of  "  transitional  epithelium."  (This  term,  introduced  by  Henle 
(Allg.  Anat.,  1841)  as  a  designation  for  epithelia  which  are  intermediate 
between  stratified  squamous  and  simple  columnar,  such  as  occur  at  the 
cardia  and  elsewhere,  is  now  generally  restricted  to  the  peculiar  epithelium 
of  the  bladder,  ureter  and  renal  pelvis.) 

The  bladder  consists  of  a  mucosa,  submucosa,  muscularis  and  serosa. 
The  epithelium  has  been  described  as  two-layered  in  the  distended  bladder, 
the  outer  cells  having  terminal  bars;  in  the  contracted  condition  it  becomes 
several-layered  and  the  bars  form  a  net  extending  into  the  epithelium. 
Thus  it  is  not  believed  that  during  distention  the  layers  shown  in  Fig.  322 
merely  flatten;  they  are  thought  to  "slip  by  each  other."  The  columnar 
cells  may,  however,  become  extremely  flat.  The  appearances  of  the 
epithelium  in  the  bladder  and  ureter  of  the  dog  under  various  conditions 
of  distention  and  contraction  have  been  figured  by  Harvey  (Anat.  Record, 
1909,  vol.  3,  pp.  296-307).  The  superficial  cells  have  a  cuticular  border; 
they  often  contain  two  nuclei,  and  their  darkly  granular  protoplasm  has  been 
considered  suggestive  of  secretory  activity.  Round  or  oval  pockets  extend 
into  the  tunica  propria  (Fig.  324).  Some  of  them  have  no  lumen,  or  are 
detached  from  the  epithelium,  but  others  are  pits  containing  a  colloid 
substance.  The  pits  are  rudimentary  glands.  In  the  adult,  branched 
tubules  lined  with  cylindrical  epithelium  may  sprout  from  the  bottom  of 
the  pits,  thus  forming  true  glands.  Their  occurrence  is  limited  to  the 


BLADDER 


325 


fundus,  which  is  the  dorsally  bulging  lowest  part  of  the  bladder,  and  to 
the  neighborhood  of  the  urethral  outlet.  In  the  latter  position  they  have 
been  regarded  as  rudimentary  prostatic  glands. 

The  tunica  propria  sometimes  contains  solitary  nodules.  It  blends 
with  the  submucosa,  as  in  the  ureter,  and  contains  lymphatic  and  blood 
vessels,  the  latter  extending  very  close  to  the  epithelium. 

The  muscularis  consists  of  smooth  muscle  fibers  arranged  in  three 
interwoven  layers,  which  are  seldom  separable  in  sections.  They  are  an 
inner  longitudinal,  middle  circular  and  outer  longitudinal  layer.  The 

Pit.  Tangential  sections  of  pits.  Secretion.  Gland. 

' 


Tunica  propria.  Smooth  muscles. 

FIG.  324. — SECTION  THROUGH  THE  FUNDUS  OF  THE  URINARY  BLADDER  OF  AN  ADULT  MAN.     X  48. 

circular  fibers  are  strengthened  at  the  beginning  of  the  urethra  to  form 
the  "internal  sphincter"  of  the  bladder,  a  muscle  not  always  distinct. 

The  serosa  is  a  connective  tissue  layer  covered  with  mesothelium. 
In  the  non-peritoneal  part  of  the  bladder  it  is  replaced  by  an  adventitia 
or  fibrous  layer. 

Non-medullated  nerves,  with  scattered  groups  of  ganglion  cells,  are 
found  outside  the  muscles  and  also  among  them.  Medullated  fibers 
terminate  around  the  ganglion  cells;  others  pass  through  the  ganglia  to 
intra-epithelial  sensory  endings. 

URETHRA  (IN  THE  FEMALE). 

The  male  urethra  will  be  described  with  the  genital  organs;  only  its 
upper  portion  is  homologous  with  the  urethra  of  the  female.  The  latter 


326 


HISTOLOGY 


is  exclusively  the  outlet  of  the  urinary  tract.  The  epithelium  has  been 
variously  described  as  stratified,  with  outer  squamous  cells,  or  as  pseudo- 
stratified,  and  columnar.  It  may  be  of  different  forms  in  different  indi- 
viduals. The  lumen  is  irregularly  crescentic,  with  longitudinal  folds 
(Fig.  325).  Branched  tubular  urethral  glands  are  found  only  in  small 
numbers,  except  near  the  outlet.  Their  secretion  is  mucoid,  but  is  not 
typical  mucus.  In  the  submucosa  there  are  many  thin- walled  veins  con- 


FIG.  325- — CROSS  SECTION  OF  THE  FEMALE  URETHRA.     (Koelliker. 

d.,  Gland-like  diverticulum;  e.,  epithelium;  L.,  lumen  of  the  urethra;  m.,  striated  muscle;  s.,  corpus  spongi- 
osum,  containing  venous  spaces  (v)  and  smooth  muscle. 

stituting  the  corpus  spongiosum.  This  is  comparable  with  the  upper 
part  of  the  more  highly  developed  corpus  cavernosum  urethras  of  the  male. 
(Compare  with  Fig.  349,  p.  347.)  The  muscularis  is  a  thick  layer,  consist- 
ing of  inner  longitudinal  and  outer  circular  smooth  muscle  fibers,  among 
which  the  veins  extend,  and  connective  tissue  with  many  elastic  fibers  is 
abundant.  The  striated  constrictor  urethra  is  outside  of  the  smooth  muscle 
layer,  as  shown  in  the  figure. 

MALE  GENITAL  ORGANS. 

DEVELOPMENT  AND  GENERAL  FEATURES. 

The  discovery  that  the  Wolffian  bodies  become  a  part  of  the  genital  system  was 
made  by  Oken,  through  dissections  and  injections  of  dog  embryos  (Beitrage,  Heft  II, 


MALE  GENITAL  ORGANS  327 


1807).  Rathke  studied  these  "Oken's  bodies"  further,  and  found  more  accurately 
their  relation  to  the  epididymis  and  ductus  deferens.  Muller  (Bildungsgeschichte  der 
Genitalien,  1830)  wrongly  declared  that  they  do  not  form  the  epididymis;  but  he  dis- 
covered that  "at  the  time  when  the  Wolffian  bodies  are  most  highly  developed,  the 
germ  of  the  ovary  or  testis  lies  on  their  inner  side;  and  on  their  outer  side,  extending 
even  to  their  upper  end,  there  is  a  duct  which  does  not  connect  with  the  Wolffian 
bodies — it  appears  to  have  arisen  from  their  short  and  much  stouter  excretory  duct." 
He  saw  that  this  second  duct,  now  known  as  the  Milllerian  duct,  formed  a  part  of  the 
uterine  tubes.  In  fact  it  forms  the  entire  tubes  together  with  the  uterus  and  vagina; 
in  the  male  it  produces  interesting  vestigial  structures  which  are  constantly  present  in 
the  adult. 

The  Miillerian  duct  arises  as  an  outpocketing  of  the  coelomic  epithe- 
lium near  the  anterior  end  of  the  Wolffian  body.  The  orifice  into  the 
peritoneal  cavity  becomes  surrounded  by  irregular  folds  known  as 
fimbrice.  As  the  Miillerian  duct  grows  posteriorly  by  the  elongation 
of  its  blind  end,  it  lies  in  contact  with  the  Wolffian  duct  as  seen  in  Fig. 
326,  but  the  Wolffian  duct  does  not  contribute  toward  its  formation. 
The  two  Miillerian  ducts  reach  the  neck  of  the  bladder  side  by  side, 
and  acquire  openings  into  it  between  those  of  the  Wolffian  ducts.  Near 
the  bladder  the  two  Miillerian  ducts  fuse  with  one  another  so  that  their 
distal  part  is  represented  by  a  single  median  tube,  on  either  side  of  which 
is  a  Wolffian  duct  (Fig.  306,  B,  page  311).  In  the  female  the  united 
portion  becomes  the  vagina  and  uterus,  and  the  separate  parts  are  the 
uterine  (or  Fallopian)  tubes.  In  the  male  the  united  portion  becomes  a 
small  blind  pocket,  the  prostatic  utricle,  opening  into  the  prostatic  urethra. 
Each  fimbriated  extremity  becomes  transformed  into  the  appendix  testis, 
and  the  remaining  portion  of  the  ducts,  except  for  occasional  fragments, 
becomes  obliterated.  Thus  only  the  two  extremities  of  the  Miillerian 
ducts  are  ordinarily  permanent  in  the  male  (Fig.  328). 

The  genital  glands  in  either  sex  begin  as  a  thickening  on  the  ventro- 
medial  border  of  each  Wolffian  body  (Fig.  326).  A  section  of  this  genital 
ridge  is  shown  in  Fig.  303,  C,  page  307.  The  ridge  is  a  dense  mass  of 
mesoderm  covered  by  the  peritoneal  epithelium,  which  here  consists 
of  a  syncytium  very  closely  connected  with  the  underlying  tissue.  Ac- 
cording to  Felix  (Keibel  and  Mall's  Human  Embryology,  vol.  2)  everything 
that  is  later  developed  within  the  genital  ridge  has  a  common  origin  from 
the  peritoneal  epithelium.  The  ridge  becomes  filled  with  an  epithelial 
mass  which  then  separates  from  the  peritoneal  layer.  Beneath  the  peri- 
toneum this  mass  produces  the  dense  connective  tissue  capsule  which  sur- 
rounds the  testis,  called,  from  its  whiteness,  the  tunica  albuginea;  within 
the  genital  ridge  it  is  " quite  suddenly"  resolved  into  anastomosing  cords 
with  looser  tissue  between  them,  and  the  cords  become  the  tubules  of  the 
testis.  Allen,  in  an  earlier  account  (Amer.  Journ.  Anat.,  1904,  vol.  3, 
pp.  89-155),  likewise  finds  that  the  cells  of  the  peritoneum  and  the  under- 


328 


HISTOLOGY 


lying  mesenchyma  appear  to  form  a  continuous  protoplasmic  network, 
and  "the  stroma  cells  are  practically  identical  with  the  peritoneal  cells 
from  which  they  are  originating."  But  Allen  concludes  that  "  the  tubules 
of  the  testis  are  formed  as  solid  invaginationsof  the  peritoneum,  which 
later  become  separated  from  it,  and  grow  by  the  activity  of  their  compo- 
nent cells."  There  is,  then,  a  difference  of  opinion  as  to  whether  the 
tubules  of  the  testis  are  formed  directly  from  the  stroma  within  the 
genital  ridge  (Felix),  or  as  imaginations  from  the  peritoneal  epithelium 


FIG.  326.— FROM  A  RECONSTRUCTION  OF  A  13.6- 
MM.  HUMAN  EMBRYO.  (F.  W.  Thyng.) 

bl.,  Bladder;  f.,  fimbrise;  g.  g.,  genital  ridge;  g.  p., 
genital  papilla;  "M.  d.,  Mullerian  duct;  p., 
renal  pelvis;  r.,  rectum;  ur.,  ureter;  u.  s., 
urogenital  sinus;  W.  d.t  Wolffian  duct. 


-  o.c. 


FIG.  327. — DIAGRAM  OF  THE  DEVELOPMENT  OF 
THE  TESTIS,  BASED  UPON  FIGURES  BY  MAC- 
CALLUM  AND  B.  M.  ALLEN. 

c.,  Glomerular  capsule;  i.  c.,  inner  or  sex  cords; 
M.  d.,  Mullerian  duct;  o.  c.,  outer  or  rete 
cords;  W.  d.,  W.  t.,  Wolffian  duct  and  tubule. 


(Allen).  A  figure  of  an  ii-mm;  human  embryo  published  by  Felix  ap- 
pears to  accord  with  Allen's  interpretation,  ancf  such  a  condition  is  shown 
diagrammatically  in  Fig.  327. 

As  the  cords  become  detached  from  the  peritoneum,  they  form  arching 
anastomoses,  convex  toward  the  periphery  of  the  ridge;  and  with  further 
growth  they  become  greatly  convoluted.  They  acquire  lumens,  and 
become  the  tubuli  contorti,  in  the  walls  of  which  spermatogenesis  takes 
place.  The  shapes  presented  by  these  tubules  in  the  embryo  have  been 
carefully  modelled  by  Bremer  (Amer.  Journ.  Anat.,  1911,  vol.  n,  pp. 
393-416). 

Toward  the  interior  of  the  genital  ridge  the  cords  become  more  slender 
and  converge  toward  the  Wolffian  body.  There  they  are  imbedded  in  a 
considerable  mass  of  tissue,  which  in  the  adult  becomes  the  mediastinum 
testis.  The  inner  ends  of  the  contorted  tubules,  toward  the  mediastinum, 
remain  straight,  forming  the  tubuli  recti;  and  these,  further  inward,  become 
thin- walled  and  anastomose  freely,  thus  constituting  the  rete  testis  (Fig. 
328). 


MALE  GENITAL  ORGANS 


329 


All  the  tubules  thus  far  considered  are  produced  by  the  genital 
ridge.  Their  inner  ends,  which  form  the  rete,  acquire  openings  into 
the  capsules  of  the  degenerating  Wolffian  glomeruli,  or  sometimes  directly 
into  a  Wolffian  tubule.  From  ten  to  fifteen  Wolffian  tubules  thus  become 
connected  with  the  rete  testis,  and  serve  to  convey  the  genital  products 
to  the  Wolffian  duct;  these  tubules  are  known  as  the  ductuli  ejferentes. 
In  the  adult  each  of  them  is  a  greatly  convoluted  tube  which  if  straightened 
measures  8  inches  (20  cm.).  When  coiled,  it  forms  a  conical  mass  or 
lobule  of  the  epididymis,  with  its  apex  toward  the  rete,  and  its  base  toward 


prostatic  gland. 


urethra 

appendix  epididymidis 
.appendix    testis 


.convoluted  tubule 


straight  tubule 


utncidus  prostaticus 
bulbourethral  gland 


para  didymis 
ductnlus     efferens 

rete  testis 

ductnlus   aberrans 
dnctus  epididymidis 


FIG.    328.— DIAGRAM   OF   THE   MALE    SEXUAL    ORGANS.     (Modified    from   Eberth,   after  Waldeyer.) 
(The  course  of  the  Mullerian  duct  is  indicated  by  dashes.) 

the  Wolffian  duct  which  it  enters  (Fig.  328).  The  Wolffian  duct,  which 
passes  along  the  dorsal  surface  of  the  testis,  is  also  greatly  convoluted  so 
that  it  measures  about  20  feet  when  straight  (6-7  meters).  Together  with 
the  efferent  ducts  this  coiled  mass  constitutes  the  epididymis  (Gr.  mt 
upon;  Si8v/xo?,  testis).  Along  the  testis  the  Wolffian  duct  is  called  the 
ductus  epididymidis,  and  from  the  testis  toward  the  urogenital  sinus  it 
is  named  the  ductus  deferens.  Near  its  termination  a  saccular  outgrowth, 
like  a  distended  gland,  develops  from  each  Wolffian  duct.  It  is  called 
the  seminal  vesicle,  and  that  portion  of  the  Wolffian  duct  between  the 
duct  of  the  vesicle  and  the  urethra  is  named  the  ejaculatory  duct.  Thus 


330  HISTOLOGY 

the  Wolffian  duct  is  arbitrarily  divided  in  the  adult  into  three  parts,  the 
ductus  epididymidis,  ductus  deferens,  and  ductus  ejaculatorius. 

It  has  been  noted  that  only  10-15  of  the  Wolffian  tubules  persist  as 
efferent  ducts;  in  man,  according  to  Felix,  these  are  the  fifty-eighth  to 
seventieth  out  of  a  series  of  eighty-  three  which  develop.  Thus  a  great 
qr>rl  ™*fgm  appendages  of  the  epididymis  arejsxrjlained 


as  persistent  rem™*"1!;*  The  appendix  epididymidis  may  represent  a 
part  of  the  Wolffian  duct  or  an  anterior  tubule  (Fig.  328);  its  history 
is  still  obscure.  Other  anterior  tubules  may  be  retained  as  appendages 
of  the  rete.  The  paradidymis  is  "a  functionless  remnant  of  the  Wolffian 
body,"  situated  behind  the  head  or  upper  end  of  the  epididymis  and  in 
front  of  the  cord  of  veins  which  accompany  the  ductus  deferens. 

Giraldes  first  described  it  (Bull.  Soc.  Anat.  Paris,  1857)  and  Koelliker  named  it  the 
"organ  of  Giraldes";  Henle  called  it  the  paraepididymis  (i.e.,  the  organ  beside  the  epi- 
didymis), and  Waldeyer  later  shortened  the  term  and  changed  its  meaning.  Felix 
(loc.  cit.,  19  1  2)  -contrary  to  the  earlier  descriptions,  places  the  paradidymis  "between 
the  epididymis  and  the  testis,  slightly  below  the  head  of  the  epididymis."  Toldt 
(Verh.  Anat.  Gesellsch,  1892,  pp.  241-242)  recognized  two  forms  of  paradidymis,  but 
both  are  behind  the  epididymis  and  in  front  of  the  veins  of  the  spermatic  cord.  The 
precise  origin  of  these  tubules  from  the  Wolffian  body  has  not  been  determined. 

Other  remains  of  the  Wolffian  body,  apparently  derived  from  the 
tubules  below  those  which  become  efferent  ducts,  are  known  as  aberrant 
ducts  (ductuli  aberr  antes).  There  may  be  two  or  three  of  them;  usually 
there  is  said  to  be  but  one.  It  proceeds  from  the  duct  of  the  epididymis, 
or  rarely  from  the  ductus  deferens  at  its  junction  with  the  duct  of  the 
epididymis,  and  terminates  in  a  coiled  mass,  sometimes  having  branches. 
The  length  of  the  aberrant  duct  is  "4-36  cm.,  generally  5-8  cm."  (Henle). 

The  External  Genital  Organs.  After  the  cloaca  has  been  divided  into 
ventral  and  dorsal  portions  by  the  downward  growth  of  the  perineal  sep- 
tum, the  ventral  portion  below  the  outlets  of  the  Wolffian  ducts  is  called 
the  urogenital  sinus.  It  receives  both  urinary  and  genital  products,  and 
in  the  male  it  forms  all  of  the  urethra  below  the  orifices  of  the  ejaculatory 
ducts.  In  the  young  embryo,  the  distal  part  of  the  urogenital  sinus  be- 
comes laterally  compressed  so  that  it  forms  an  epithelial  plate.  This 
plate  reaches  the  external  surface  of  the  body  along  the  mid-ventral  line 
of  an  elevation  known  as  the  genital  papilla  (or  tubercle).  The  genital 
papilla  (Fig.  326)  becomes  very  prominent  in  embryos  of  both  sexes.  In 
the  male  it  continues  its  development  and  forms  the  penis,  along  the  under 
side  of  which  the  urogenital  sinus  acquires  a  cleft-like  opening  (Fig.  329, 
A).  This  elongated  aperture  closes  from  behind  forward,  along  the  line 
permanently  marked  by  a  raphe  (or  seam).  In  the  abnormal  cases  of 
hypospadias,  the  urogenital  sinus  retains  a  more  or  less  extensive  opening 
on  the  under  side  of  the  penis.  A  rounded  terminal  glans  is  early  differen- 


MALE    GENITAL   ORGANS 


331 


tiated  at  the  apex  of  the  genital  papilla.  The  epidermis  is  adherent  to  it, 
but  later  becomes  separated  by  the  formation  and  splitting  of  an  epithe- 
lial plate,  thus  producing  the  reflection  of  skin  called  the  prepuce.  The 
urogenital  sinus  becomes  secondarily  prolonged  through  the,glans  so  as 
to  form  the  terminal  part  and  external  orifice  of  the  urethra.  The  entire 
urethra  is  divided  into  three  parts:  (i)  the  prostatic  portion  (pars  pros- 
tatica),  which  includes  the  outlet  of  the  bladder  together  with  the  upper 
end  of  the  urogenital  sinus,  and  receives  the  ejaculatory  and  prostatic 
ducts;  (2)  the  membranous  part  (pars  membranacea) ,  which  is  the  short 
dilatable  portion  traversing  the  "pelvic  diaphragm";  and  (3)  the  long 
cavernous  portion  (pars  cavernosa),  which  is  surrounded  by  the  cavern- 
ous vascular  tissue. 

The  scrotum  develops  as  a  median  pouch  at  the  dorsal  end  of  the  uro- 
genital raphe.  It  is  continuous  above  with  the  pair  of  large  genital  folds 
which  tend  to  encircle  the  base  of  the  genital  papilla,  being  deficient  only 
below  (Fig.  329,  A).  At  the  stage  when  the  testis  and  Wolffian  body  are 


FIG.  329. — A,  DIAGRAM  OF  THE  EMBRYONIC  EXTERNAL  GENITAL  ORGANS  IN  THB  MALE;  B,  C,  D,  DIAGRAMS 
OF  THE  DESCENT  OF  THE  TESTIS.  (After  Eberth.) 

a.,  Anus;  ep.,  epididymis;  g.,  glans  penis;  g.  f.,  lesser  genital  folds;  g.  g.  f.,  greater  genital  folds;  p.  c.,  peri- 
toneal cavity;  p.  v.,  processus  vaginalis;  r.,  raphe;  t.,  testis;  p.  L,  parietal  layer  of  the  tunica  vagmalis; 
u.  s.,  urogenital  sinus;  v.  1.,  visceral  layer  of  the  tunica  vagmalis. 

still  within  the  abdomen,  lying  behind  the  peritoneum,  the  peritoneal 
cavity  sends  a  prolongation,  the  processus  vaginalis,  over  the  pubic  bone 
into  each  half  of  the  scrotum  (Fig.  329,  B).  A  large  retroperitoneal 
column  of  connective  tissue,  the  gubernaculum  testis,  extends  from  the 
posterior  end  of  each  testis  into  the  depth  of  the  scrotum.  For  reasons 
still  obscure,  such  a?  unequal  growth  or  the  shortening  of  this  cord,  the 
testes  pass  down  in  front  of  the  pubic  bones,  into  the  scrotum  (Fig.  329, 
C).  The  Wolfiian  duct  becomes  bent  over  the  ureter  as  shown  in  Fig.  328, 
and  this  important  relation  is  found  in  the  adult.  Except  on  its  dorsal 
border,  the  testis  is  closely  invested  by  the  peritoneum  of  the  processus 
vaginalis.  Later  the  distal  part  of  the  processus  becomes  separated  from 
the  abdominal  cavity  by  the  obliteration  of  its  stalk.  The  part  remain- 
ing about  the  testis  is  the  tunica  vaginalis ,  having  a  parietal  and  a  visceral 
layer  as  shown  in  Fig.  329,  D.  The  descent  of  the  testes  is  completed 
shortly  before  birth,  except  in  the  occasional  cases  of  "undescended  testis." 


332 


HISTOLOGY 


TESTIS. 

Septa,  Vessels,  and  Nerves.  The  general  arrangement  of  the  parts  of 
the  testis,  as  they  appear  in  cross  section,  is  shown  in  Fig.  330.  From 
the  tunica  albuginea,  small  connective  tissue  septa  (septula  testis)  pass  to 
the  mediastinum,  dividing  the  testis  into  "100-200"  pyramidal  lobules 
with  their  apices  toward  the  rete.  The  tunica  albuginea  is  a  dense  con- 
nective tissue  layer,  containing  numerous  elastic  fibers  which  increase  in 
abundance  with  age.  Its  outer  surface  is  covered  with  the  visceral  layer 
of  the  tunica  vaginalis.  The  inner  portion  of  the  albuginea  is  very  vascu- 
lar, forming  a  distinct  layer  at  birth  (the  tunica  vasculosa). 


Ductus  deferens. 
Blood  vessels. 


Straight  tubules. 


Mediastinum, 

containing  the 

rete  testis. 


Lobules,  con- 

•.-»•  i   .-/ — rsisting  of  con- 

' *J  |  'JL*^"      voluted  tubules. 

i-^r/ 


Tunica 
vasculosa. 

Tunica 
albuginea. 


FIG.  330. — CROSS  SECTION  OF  THE  TESTIS  OF  A  CHILD  AT  BIRTH.     X  10. 


Connective  tissue  extends  from  the  septula  among  the  convoluted 
tubules.  Immediately  surrounding  them  there  is  a  delicate  basement 
membrane,  followed  by  a  layer  of  closely  interwoven  elastic  fibers  and 
flat  cells.  In  the  looser  connective  tissue  between  the  tubules,  there  are 
clumps  of  interstitial  cells  (Figs.  331  and  335),  which  arise  from  mesenchy- 
mal  cells  of  the  genital  ridge.  Sometimes  they  retain  protoplasmic  proc- 
esses, but  more  often  they  are  rounded  or  polygonal  structures  in  close 
contact,  and  without  distinct  cell  boundaries.  In  their  abundant  proto- 
plasm there  are  pigment  and  other  granules,  fat  droplets,  and  rod-shaped 


TESTIS  333 

crystalloids,  the  significance  of  which  is  unknown.  The  nature  of  the 
granules  is  discussed  by  Whitehead  (Amer.  Jo  urn.  Anat,  1912,  vol.  14 
pp.  63-71). 

The  interstitial  cells,  although  not  intimately  related  with  the  vessels, 
are  thought  to  produce  an  internal  secretion,  and  certain  observations 
suggest  that  the  sexual  instinct  is  dependent  on  these  cells  rather  than 
upon  the  spermatozoa  (cf.  Whitehead,  Anat.  Rec.,  1908,  vol.  2,  pp.  177- 
182).  During  senile  atrophy  of  the  testis,  the  interstitial  cells  at  first 
increase;  later  they  are  destroyed..  At  the  same  time  the  basement  mem- 
brane becomes  thickened  and  hyaline,  fat  droplets  accumulate,  and  the 
sexual  cells  disappear  from  the  tubules,  leaving  the  sus  tentacular  cells. 

The  arteries  of  the  testis  are  branches  of  the  internal  spermatic  artery, 
which  descends  through  the  spermatic  cord,  beside  the  ductus  deferens. 
The  branches  enter  the  testis  in  part  through  the  mediastinum,  and  in 


Interstitial  cells. 


Connective  tissue. 


*•  ' 


Mfe 

".£•-•  'y.^-.-S..^^^:^ 

^•; ~-' ....".  .* .  V  4  ' .  »-\ w^jfM^^^W 

FIG.  331- — FROM  A  CROSS  SECTION  OF  THE  TESTIS  OF  A  MAN  TWENTY-TWO  YEARS  OLD.     X  so. 

part  through  the  tunica  vasculosa.  They  extend  through  the  septula, 
and  form  capillary  plexuses  around  the  convoluted  tubules.  The  veins 
accompany  the  arteries.  Lymphatic  vessels  are  numerous  in  the  tunica 
albuginea  and  extend  among  the  tubules.  Nerves  from  the  spermatic 
plexus  surround  the  blood  vessels;  the  presence  of  intraepithelial  endings 
has  not  been  established  with  certainty. 

Convoluted  Tubules.  The  shape  of  the  tubules  of  the  testis  has  been 
repeatedly  investigated,  but  whether  blind  ends  occur  has  not  been 
established;  generally  the  tubules  end  in  loops.  Anastomoses  have  been 
recorded,  not  only  between  the  tubules  in  a  single  lobule,  but  also  between 
adjacent  lobules.  The  extent  of  the  anastomoses  among  the  closely 
coiled  tubules  is  difficult  to  determine. 

For  more  than  seventy  years  eminent  anatomists  have  recorded  their  success  or 
failure  in  finding  blind  ends— Krause,  Kolliker,  Sappey  and  LaValette  St.  George 
state  that  they  exist;  Hyrtl,  Henle,  Mihalkovics  and  Eberth  fail  to  find  them.  Two 


334 


HISTOLOGY 


recent  papers  have  dealt  with  the  subject.  Bremer  (1911)  concludes  that  the  tubules 
may  end  blindly;  Huber  and  Curtis  (1913)  state  that  the  seminiferous  tubules  in  the 
rabbit  present  no  blind  ends. 

The  convoluted  tubules  are  lined  with  a  highly  specialized  stratified 
epithelium  (Fig.  332).  The  cells  divide  and  differentiate  as  they  pass 
from  the  basal  layer  outward.  Finally  each  outer  cell  produces  a  single 


Spermatids. 

Sustentacular  cell. 

Spermatogonium . 


Blood  vessel  with 
blood  corpuscles. 


Spermatids. 


Sustentacular  cell. 


Spermatogonia,  beneath 
large  spermatocytes. 


Sustentacular  cells. 


FIG.  332. — CROSS  SECTIONS  OF  SEMINIFEROUS  (CONVOLUTED)  TUBULES  OF  A  MOUSE.     X  360. 

large  cilium,  or  flagellum,  projecting  from  the  free  surface,  and  becomes 
detached  as  a  spermatozoon.  The  process  of  transformation  of  the  basal 
cells,  or  spermatogonia,  into  spermatozoa  is  known  as  spermatogenesis. 
Its  cytological  features,  as  observed  in  the  testis  of  the  grasshopper, 
have  already  been  described  (p.  21).  Ordinary  sections  of  the  human 
testis  present  the  following  characteristics: 

Each  tubule  is  composed  of  cells  of  two  sorts — sexual  cells  and  susten- 
tacular  cells.  At  birth  the  cords  and  developing  tubules  contain  relatively 
few  sexual  cells  (Fig.  333).  These  are  characterized  by  their  large  size, 
clear  protoplasm,  and  round  vesicular  nuclei.  It  is  said  that  they  retain 
a  primitive  granular  arrangement  of  their  mitochondria.  These  cells 
multiply  by  ordinary  mitosis,  producing  the  spermatogonia.  Thus  the 
sexual  cells  in  various  forms  eventually  far  outnumber  the  Sustentacular 
cells. 


TESTIS 


335 


The  sexual  or  genital  cells  are  apparently  produced  from  the  cords  in  the  testis, 
relatively  late  in  embryonic  development.  It  was  suggested  by  Nussbaum,  however, 
that  the  sexual  cells  are  set  apart  much  earlier — "they  do  not  come  from  any  cells 
that  have  given  up  their  embryonic  character  or  gone  into  building  any  part  of  the 
body."  In  accordance  with  this  idea,  it  is  considered  by  some  authorities  that  in  the 
segmentation  stages,  a  line  of  undifferentiated  cells  is  set  apart  to  become  the  sexual 
cells,  add  that  from  the  beginning  they  are  distinct  from  the  somatic  cells  which  form 
the  rest  of  the  body.  As  stated  by  Allen  (Journ.  Morph.,  1911,  vol.  22,  pp.  1-36), 
the  sexual  cells  do  not  belong  to  any  one  germ  layer;  they  are  free  to  follow  their  own 
path  in  their  travels  from  the  place  of  origin  to  the  genital  glands  where  they  finally 
come  to  rest.  Thus  the  sexual  cells  have  been  reported  as  distributed  somewhat 
diffusely  in  the  entoderm  and  mesoderm.  (For  papers  on  this  subject,  see  Allen, 
Anat.  Anz.,  1906,  vol.  29,  pp.  217-236.)  In  a  human  embryo  of  2.6  mm.  Felix  found 
seven  of  these  large  clear  cells,  all  in  the  immediate  vicinity  of  the  cloaca.  Another 
embryo  of  2.5  mm.,  showed  twelve  "primary  genital  cells."  But  he  adds  that  they  all 
disappear  in  later  stages,  and  when  the  genital  glands  are  formed  there  are  no  genital 
cells.  At  present  it  has  by  no  means  been  demonstrated  that  the  mammalian  sexual 
cells  are  not  differentiated  products  of  the  testis  or  ovary,  adapted  for  the  special  pur- 
pose of  reproduction. 


FIG.  333- — CROSS  SECTION  OF  A  CONVOLUTED 
TUBULE  OF  THE  TESTIS  AT  BIRTH. 
(Eberth.) 


FlG.  334. SUSTENTACULAR  C-ELLS. 

a.,  Isolated     (Koelliker);     b.,     Gplgi     preparations. 
(Bohm  and  von  Davidoff.) 


The  sustentacular  or  supporting  cells,  often  called  Sertoli's  cells,  are 
at  first  indifferent  cells  forming  a  syncy tium  (Fig.  333) .  With  the  increase 
in  the  number  of  spermatogonia,  their  protoplasm  is  resolved  into  a 
network  of  strands,  molded  by  the  surrounding  cells  (Fig.  334).  Their 
nuclei  are  radially  compressed  into  ovoid  shapes,  and  lie  in  columns  of 
protoplasm  extending  from  the  periphery  of  the  tubule  toward  its  lumen. 
Each  nucleus  has  a  distinct  nucleolus,  apart  from  which  its  chromatic 
material  is  very  scanty.  Usually  the  nuclei  are  in  the  lower  half  of  the 
branching  protoplasmic  columns,  the  polygonal  bases  of  which  are  in 
contact  with  one  another  beneath  the  spermatogonia.  Within  the  proto- 
plasm fat  droplets  occur,  together  with  brown  granules;  crystalloid 
bodies  in  pairs  may  also  be  found.  As  seen  in  Fig.  334,  a,  the  heads  of 
the  spermatozoa  appear  attached  to,  or  imbedded  in,  the  protoplasm 
of  the  sustentacular  cells,  which  are  supposed  to  nourish  them.  The 


336  HISTOLOGY 

spermatozoa  may  be  gathered  in  characteristic  clumps  at  their  upper  ends 
(Fig.  332). 

In  ordinary  sections  of  the  testis,  the  sustentacular  cells  may  be  recog- 
nized by  their  distinctive  nuclei  (Fig.  335).  The  sexual  cells  in  the  basal 
row  are  presumably  spermatogonia.  Above  them  are  the  spermatocytes, 
which  are  larger;  their  nuclei  usually  show  spiremes  or  other  indications 
of  cell  division.  Secondary  spermatocytes  are  further  out  than  the  pri- 
mary spermatocytes;  and  above  them  are  the  spermatids  in  various 
stages  of  transformation  into  spermatozoa.  Since  spermatogenesis  occurs 
in  "waves,"  the  outer  cells  in  a  tubule  cut  lengthwise  form  a  succession  of 
zones,  each  of  which  shows  gradations  from  young  spermatids  to  mature 
spermatozoa;  a  single  zone  is  included  in  Fig.  335.  In  transverse  sections 
all  the  superficial  cells  may  be  of  one  stage,  which  differs  from  that  in 
the  adjoining  tubule  (Fig.  332). 

Heads  of  ,_ 
spermatozoa. 


Spermatocyte. ^_    ^   .      w  _  .«       ^       «*    v 

Nuclei  of 
tentacular  cells. 


Crystalloids  in 
interstitial 

cells.  ''(&-'    &'*' <**)&-  -S -^*~^~~  ^\   Interstitial  con- 

nective tissue. 

FIG.  335—  FROM  A  LONGITUDINAL  SECTION  THROUGH  A  CONVOLUTED  TUBULE  OF  A  HUMAN  TESTIS.    X  360. 

Stages  in  the  transformation  of  a  spermatid  into  a  spermatozoon  are 
shown  in  the  diagram  Fig.  336.  The  chromosomes  of  the  spermatid 
disappear  in  a  dense  chromatic  network  which  becomes  apparently  homo- 
geneous. This  deeply  staining  nucleus  passes  to  one  end  of  the  protoplasm 
of  the  spermatid.  It  becomes  the  essential  part  of  the  head  of  the  sper- 
matozoon, which  in  man  is  a  flattened  structure,  oval  on  surface  view, 
and  pyriform  with  its  apex  forward  when  seen  on  edge  (Fig.  337).  The 
head  is  at  the  anterior  end  of  the  spermatozoon,  which  during  its  develop- 
ment is  directed  toward  the  basal  layers  of  the  convoluted  tubule.  The 
anterior  end  of  the  head  is  probably  covered  by  a  thin  layer  of  protoplasm, 
known  as  the  galea  capitis.  The  archoplasm  of  the  spermatid  (known  as 
the  idiozome)  is  said  to  leave  the  centrosome  and  to  enter  the  protoplasm 
of  the  galea  capitis,  where  it  forms  the  perforatorium.  If  this  exists  in 
man,  it  is  in  the  form  of  a  cutting  edge  following  the  outline  of  the  front 
of  the  head;  in  other  animals  the  perforatorium  may  be  a  slender  spiral 
or  barbed  projection,  which  enables  the  spermatozoon  to  penetrate  the 
ovum. 


TESTIS 


337 


The  protoplasm  of  the  spermatid  forms  an  elongated  mass  at  the  pos- 
terior end  of  the  nucleus.  It  contains  the  centrosome  which  soon  divides 
in  two.  Of  these  the  anterior  forms  a  disc  which  becomes  adherent  to 
the  nuclear  membrane.  The  poste- 
rior centrosome  also  becomes  a  disc 
after  giving  rise  to  a  motile  axial 
filament,  which  grows  out  from  it  like 
a  cilium.  The  disc-like  centrosome 
attached  to  the  anterior  end  of  the 
filament  becomes  thin  in  such  a  way 
that  its  peripheral  portion  is  detached, 
and  as  a  ring  surrounding  the  fila- 
ment it  passes  to  the  posterior  limit 
of  the  protoplasm.  The  protoplasm 
between  the  two  parts  of  the  poste- 
rior centrosome  is  reduced  to  a  thin 
layer  in  which  a  spiral  filament  de- 
velops, winding  about  the  axial  fila- 
ment. Distal  to  the  centrosome  ring, 
the  axial  filament,  which  consists  of 
fine  fibrils,  is  surrounded  by  a  thin 
membrane,  which  terminates  or  be- 
comes very  thin  near  the  extremity 
of  the  filament.  This  membrane, 
which  in  salamanders  forms  a  conspicuous  undulating  frill,  is  thought  to 
be  a  product  of  the  filament  and  not  an  extension  of  the  protoplasm. 
In  man  it  is  inconspicuous,  and  many  of  the  details  here  described  can 
be  made  out  only  under  most  favorable  conditions.  The  preceding  ac- 
count is  based  on  studies  of  the  guinea-pig  (Meves, 
Arch.  f.  mikr.  Anat.,  1909,  vol.  73,  pp.  751-792). 

Mature  spermatozoa  are  divided  into  three 
parts — the  head,  neck,  and  tail.  The  head  (3-5  /* 
long  and  2-3  /*  wide)  includes  the  nucleus,  gale  a 
capitis  and  perforatorium.  The  neck  consists  of 
the  anterior  centrosome  and  the  substance,  not 
traversed  by  the  axial  filament,  between  it  and 
the  posterior  centrosome.  The  neck  in  man  is 
not  constricted  as  in  some  forms,  yet  it  is  a  place 
where  the  head  may  become  detached.  The  tail 
includes  three  parts,  the  connecting  piece,  chief  piece 

and  end  piece.  The  connecting  piece  (6  n  long  and  scarcely  i  /*  wide) 
consists  of  protoplasm,  axial  and  spiral  filaments,  and  the  two  parts  of 
the  posterior  centrosome.  The  chief  piece  (40-60  n  long)  is  the  axial 

22 


FIG.  336. — DIAGRAMS  OF  THE  DEVELOPMENT  OF 
SPERMATOZOA.  (After  Meves.) 

a.  c.,  anterior  centrosome;  a.  f.,  axial  filament; 
c.  p.,  connecting  piece;  ch.  p.,  chief  piece;  g.  c., 
galea  capitis;  n.,  nucleus;  nk.,  neck;  p.,  pro- 
toplasm; p.  c.,  posterior  centrosome. 


FIG.   337. — SPERMATOZOA:    i, 

2,  3,  HUMAN  4,  FROM  A  BULL. 

a,  Head;  b,  connecting  piece, 

and  c,  chief  piece  of  the 

tail,     i,  3,  and  4,  Surface 

views 52,  side  view.     X  360 


338  HISTOLOGY 

filament  with  its  surrounding  membrane;  and  the  end  piece  (10  /<)  is 
a  prolongation  of  the  filament.  When  the  spermatozoa  become  free  they 
float  in  the  albuminous  fluid  secreted  in  small  quantity  by  the  tubules  of 
the  testis.  They  pass  through  the  straight  tubules  and  rete  to  the  epi- 
didymis,  in  which  they  accumulate,  and  where  they  first  become  motile. 
Their  motility  is  greater,  however,  in  the  seminal  fluid,  which  is  a  mixture 
of  the  products  of  the  epididymis,  seminal  vesicles,  prostate  and  bulbo- 
urethral  glands.  By  an  undulating  movement  of  the  tail,  the  head  is 
propelled  forward,  always  being  directed  against  such  a  current  as  is  made 
by  cilia,  at  a  rate  of  J  of  an  inch  in  a  minute.  Water  inhibits  the  motion, 
which  is  favored  by  alkaline  fluids;  it  occurs  also  in  those  faintly  acid. 
For  three  days  after  death  spermatozoa  may  retain  their  activity  in  the 
seminal  passages;  in  the  female  urogenital  tract  they  may  live  a  week 
or  more.  In  addition  to  normal  spermatozoa,  giant  forms,  and  some 
with  two  heads  or  two  tails  occur,  but  these  are  probably  functionless 
abnormalities.  The  production  of  spermatozoa,  beginning  at  puberty, 
continues  throughout  life,  but  with  advancing  age  the  rate  diminishes. 
Since  about  60,000  spermatozoa  occur  in  a  cubic  millimeter  of  seminal 
fluid,  it  has  been  estimated  that  340  billions  are  produced  in  a  lifetime. 

•  The  discovery  of  spermatozoa  was  reported  to  the  Royal  Society  of  London,  in  1 6  7  7 , 
by  Leeuwenhoek.  They  were  first  seen  by  Dr.  Ham,  "a man  of  singular  modesty," 
to  whom  Leeuwenhoek  gives  full  credit  for  the  discovery  in  his  letters  to  the  Royal 
Society.  He  wrote  as  follows: 

"This  discerning  youth  visited  me  and  brought  with  him,  in  a  small  glass  vial, 
seminal  fluid  from  a  man  who  had  cohabited  with  a  diseased  woman;  and  he  stated  that 
after  some  minutes  when  the  fluid  had  become  so  attenuate  that  it  could  be  put  in  a 
slender  glass  tube,  he  had  seen  living  animalcules  in  it,  which  he  thought  were  pro- 
duced by  some  putrefaction.  He  added  that  those  animalcules  seemed  to  him  to  be 
provided  with  tails,  and  that  they  did  not  survive  the  space  of  twenty-four  hours. 
Moreover  he  declared  that  when  terebinth  had  been  given  to  the  patient  internally,  the 
animalcules  appeared  to  be  dead. 

"I  poured  this  material  in  a  glass  tube  and  examined  it  in  the  presence  of  Dr.  Ham, 
and  saw  some  live  animalcules  in  it.  But  when  after  two  or  three  hours,  I  examined 
the  material  more  carefully,  by  myself,  I  saw  that  all  the  animalcules  were  dead." 

Leeuwenhoek  diligently  pursued  the  study  of  these  animalcules,  and  found  them  in 
enormous  numbers  in  the  semen  of  insects,  fishes,  birds  and  quadrupeds.  He  estimated 
that  there  were  150,000,000,000  in  the  milt  of  one  fish,  or  more  than  ten  times  the  num- 
ber of  men  then  living  (13,385,000,000  homines  in  orbe  terrarum).  Leeuwenhoek  be- 
lieved that  the  animalcules  were  of  two  sexes,  and  that  the  egg  consisted  of  a  fluid  in 
which  they  swam  about  and  developed.  To  some  it  seemed  not  unreasonable  that  new 
individuals  should  be  enclosed  in  the  spermatozoa,  like  an  insect  in  its  chrysalis,  and 
Dalenpatius  (1699)  thought  that  he  could  observe  them.  As  quoted  by  Vallisneri,  he 
wrote  as  follows,  illustrating  his  account  with  the  figure  here  reproduced  (Fig.  338). 

'"We  have  seen  some  animalcules  having  just  the  form  of  tadpoles  such  as  are  found 
in  brooks  and  muddy  bogs  in  the  month  of  May.  The  tail  is  four  or  five  times  as  long 
as  the  body.  They  move  with  wonderful  rapidity  and  by  the  strokes  of  their  tails  pro- 


TESTIS  339 

duce  little  waves  in  the  substance  in  which  they  swim.  But  who  would  believe  that  in 
these  a  human  body  was  hidden?  Yet  we  have  seen  such  with  our  own  eyes.  For 
while  we  were  observing  them  attentively,  a  large  one  threw  off  its  surrounding  mem- 
brane and  appeared  naked,  showing  distinctly  two  legs,  thighs,  breasts  and  arms.  The 
cast-off  skin,  drawn  upward,  covered  the  head  like  a  cap,  and  it  was  a  delightful  and 
incredible  sight.  Because  of  the  minuteness  of  the  object,  the  sex  could 
not  be  distinguished.  After  the  little  creature  had  lost  its  membrane  it 
soon  died." 

This  is  a  gross  presentation  of  the  preformation  theory,  according  to 
which  the  various  parts  of  the  adult  are  represented  in  the  very  young 
embryo.  It  was  held  by  many  who  could  not  verify  such  observations. 
An  alternative  theory  is  that  of  epigenesis,  according  to  which  the.  body  FlGi  338. 
and  its  parts  arise  out  of  formless  substance.  Descartes  (1664)  wrote 
that  the  source  of  a  new  individual  "seems  to  be  only  a  confused  mixture  of 
liquors,  which,  serving  to  leaven  one  another,  become  heated;  some  of  their  agitated 
particles  dilate,  and  press  upon  the  others,  gradually  disposing  them  in  the  way  neces- 
sary to  form  organs."  Such  physico-chemical  speculations,  however,  are  quite  as 
imaginative  as  any  views  of  the  preformationists  and  Descartes's  epigenesis  was  early 
characterized  as  "  a  very  lame  account  of  the  forming  of  an  animal."  Nevertheless, 
the  doctrine  of  epigenesis,  as  advocated  by  Harvey  (1651)  and  Wolff  (1759),  prevailed 
over  the  cruder  ideas  of  preformation.  If,  however,  the  spermatozoon  can  contribute 
to  the  production  of  only  one  of  the  myriad  forms  of  animals,  even  the  sex  of  which  is 
apparently  predetermined,  it  is  evident  that  the  spermatozoon  must  possess  a  very 
definite  chemical  composition,  and  perhaps  a  corresponding  ultra-microscopic  structure. 
Doubtless  there  is  a  preformation  no  less  remarkable  than  that  expressed  through 
the  active  imagination  of  Dalenpatius. 

Tubuli  Recti  and  the  Rete.  The  large  convoluted  tubules,  are  140  ju 
in  diameter.  As  they  pass  toward  the  epididymis  they  decrease  in  size; 
they  receive  branches  at  acute  angles  and  their  windings  diminish. 
Sex-ual  cells  disappear,  leaving  only  the  sustentacular  cells  in  the  form  of  a 
simple  columnar  epithelium.  This  flattens  abruptly  to  form  the  lining  of 
the  straight  tubules.  Both  the  straight  tubules  and  the  rete  are  lined 
with  a  simple  epithelium  of  low  cells.  In  some  places  these  are  very  flat, 
suggesting  endothelium;  in  others  they  are  columnar.  The  characteristic 
dilatations  of  the  rete  tubules  are  shown  in  Fig.  339.  They  contain 
spermatozoa  and  immature  sexual  cells  together  with  pigment  granules 

and  broken  down  cells. 
i 

EPIDIDYMIS. 

The  efferent  ducts,  which  pass  from  the  rete  to  the  duct  of  the  epididy- 
mis, are  lined  with  an  epithelium  in  which  groups  of  columnar  cells  alter- 
nate with  those  which  are  cuboidal  (Figs.  340  and  341).  Thus  the  inner 
surface  of  the  epithelium  has  depressions  suggesting  glands,  but  the  basal 
surface  is  free  from  outpocketings.  The  epithelium  is  generally  simple, 
although  in  the  tall  parts  it  may  appear  two  or  three  layered.  The  cells 
contain  fat,  pigment,  and  other  granules,  and  produce  a  secretion  which 


340 


HISTOLOGY 


FIG.  339. — SECTION  OF  THE  HUMAN  RETE  TESTIS.     X  96.     (Kolliker.) 

A,  Artery;  C,  rete  tubules;  L,  lymphatic  vessels;  s,  connective  tissue  partly  surrounded  by  rete  tubules; 
Sk,  part  of  a  convoluted  tubule,  to  the  left  of  which  are  sections,  probably  of  straight  tubules;  V,  vein. 

Tangential  section 

of  a  ductulus 

efferens. 


Connective  tissue. 


Blood  vessel.       Epithelium     Circular  muscles        Transverse  section  of  a 

ductulus  efferens. 


of  the  ductus  epididymidis. 
FIG.  340. — FROM  A  SECTION  OF  THE  HEAD  OF  A  HUMAN  EPIDIDYMIS,  SHOWING  SECTIONS  OF  THE  DUCTUS 
EPIDIDYMIDIS  IN  THE  CENTER,  AND  OF  DUCTULI  EFFERENTES  ON  THE  SIDES.     X  so. 


EPIDIDYMIS 


341 


Cubical  cells.        Columnar  cells. 


may  appear  in  vesicular  masses  on  the  surface  of  the  cells.  Often  the  tall 
cells,  and  occasionally  the  short  ones,  are  ciliated.  The  cilia  vibrate  so  as 
to  produce  a  current  toward  the  ductus  epididymidis.  The  epithelium 
rests  on  a  striated  basement  membrane  which  is  surrounded  by  a  layer  of 
circular  smooth  muscle  fibers,  several  cells  thick.  The  muscle  layer  is 
thickest  toward  the  ductus 
epididymidis.  Among  the 
muscle  cells  there  are  elas- 
tic fibers,  which,  like  those 
of  the  ductus  epididymidis 
and  ductus  deferens,  first 
appear  at  puberty.  There 
are  no  glands  in  the  effer- 
ent duCtS  but  the  irregU-  Smooth  muscle  fibers.  Connective  tissue. 

FIG.  341. — TRANSVERSE  SECTION  OF  A   DUCTULUS  EFFERENS, 
laritieS    in    the    epithelium  FROM  THE  TESTIS  OF  AN  ADULT  MAN. 

The  right-hand  end  of  the  illustration  is  schematic.     No  cilia 

are    thought    tO    be  due   tO  C9uld  be  seen,  although  those  of  the  epithelium  of  the  epi- 

didymis  were  well  preserved.      X  360. 

glandular  activity.    B  ef or e 

puberty  and  in  old  age  these  irregularities  are  slight. 

The  ductus  epididymidis  consists  of  a  two-rowed  epithelium  with 
rounded  basal  cells  and  tall  outer  columnar  cells.  The  latter  contain 
secretory  granules  and  sometimes  pigment,  and  have  in  the  middle  of 
their  upper  surfaces  long  non-motile  hairs,  which  in  sections  are  usually 
matted  in  conical  processes  (Fig.  41,  6,  p.  51).  The  epithelium  may 
contain  round  cavities  opening  into  the  lumen  or.  forming  closed  cysts. 
The  delicate  membrana  propria  and  thick  circular  muscle  layer  complete 
the  -wall  of  the  ductus,  the  convolutions  of  which  occur  in  a  loose  connec- 
tive tissue.  Toward  the  ductus  deferens  the  muscle  layer  thickens. 

There  are  no  glands  in  the 
ductus  epididymidis,  but  its  cells 
produce  considerable  secrelion 
in  which  the  spermatozoa  be- 
come active. 

The  blood  vessels  of  the  epi- 
didymis,  which  are  few  in  com- 
parison with  those  of  the  testis, 

FIG.  342.-TRANSVERSE ACTION  OFgA  HUMAN  DUCTUS       lie  in  part  SQ  dose  to  the  efferent 

ducts  as  to  cause  the  membrana 

propria  to  bulge  toward  the  epithelium.  The  nerves,  besides  peri  vas- 
cular nets,  form  a  thick  plexus  myospermaticus  provided  with  sym- 
pathetic ganglia.  It  is  found  in  the  muscle  layer,  which  it  supplies, 
sending  fibers  also  into  the  mucosa.  In  the  ductus  deferens  and  seminal 
vesicles  this  plexus  is  said  to  be  more  highly  developed  than  in  the 
epididymis. 


Epithelium. 

Membrana 
propria. 

Circular   layer   of 
muscle  fibers. 

Loose    connective 
tissue. 


342 


HISTOLOGY 


..Epithelium. 


Tunica  propria. 


T      ,. 

innertlongitu- 

dinai:muscies. 


DUCTUS  DEFERENS. 

The  ductus  deferens  begins  as  a  convoluted  tube  continuous  with 
the  ductus  epididymidis;  it  becomes  straight  and  passes  to  its  termin- 
ation in  the  ductus  ejaculatorius.  Shortly  before  reaching  the  prostate  it 
exhibits  a  spindle-shaped  enlargement  or  ampulla  about  J  inch  long  and  f 
inch  wide  (Fig.  344).  The  ductus  deferens  consists  of  a  mucosa,  muscu- 
laris  and  adventitia.  The  epithelium  is  generally  in  two  rows,  the 
tall  inner  cells  producing  round  masses  of  secretion.  Toward  the  epi- 
didymis  it  may  also  have  non-motile  cilia.  Toward  the  ampulla  it  may  be 

several  rowed,  resembling  the 
epithelium  of  the  bladder. 
It  rests  on  a  connective  tissue 
tunica  propria,  which  is  sur- 
rounded by  the  three  layers 
of  the  muscularis.  The  inner 
and  outer  layers  are  longi- 
tudinal and  generally  less  de- 
veloped than  the  middle  cir- 
cular layer.  The  adventitia 
is  a  loose  elastic  connective 
tissue,  blending  with  that 
which  forms  the  spermatic 
cord.  The  latter  contains 
numerous  arteries,  veins, 
lymphatics  and  nerves,  to- 
gether with  the  striated  mus- 
cle fibers  of  the  cremaster  muscle,  and  the  rudiment  of  the  processus 
vaginalis.  The  veins  are  very  numerous  and  constitute  the  pampiniform 
plexus  (i.e.,  tendril-like).  Their  walls  are  usually  provided  with  a  very 
thick  musculature  including  both  circular  and  longitudinal  fibers. 

In  the  ampulla  the  longitudinal  folds,  which  are  low  in  the  ductus 
deferens,  become  tall  and  branched,  so  that  they  partly  enclose  irregular 
spaces  (diverticula) .  Similar  folds  occur  in  the  seminal  vesicles.  It  is 
doubtful  whether  in  either  place  any  of  the  spaces  should  be  considered 
glands.  Around  the  ampulla  the  musculature  is  irregularly  arranged;  the 
longitudinal  layers  separate  into  strands  which  terminate  toward  the 
ejaculatory  ducts. 

SEMINAL  VESICLES  AND  EJACULATORY  DUCTS. 

The  seminal  vesicles  grow  out  from  the  ductus  def erentes  at  the  prostatic 
ends  of  their  ampullae.  Each  consists  of  a  number  of  saccular  expansions 
arranged  along  the  main  outgrowth,  which  is  irregularly  coiled.  The 


FIG.  343- 


CROSS  SECTION  O^THE  HUMAN  DUCTUS  DEFERENS. 


SEMINAL  VESICLES 


343 


lining  of  the  sacs  is  honeycombed  with  folds  as  shown  in  Figs.  344  and  345. 
The  epithelium  is  generally  simple  or  two-layered,  the  height  of  the  cells 
varying  with  the  distention  of  the  vesicles  by  secretion.  Granules  occur 
in  the  cells,  which  produce  a  clear  gelatinous  secretion  in  sago-like  masses. 
Spermatozoa  are  generally  found  in  the  human  vesicles,  but  except  during 
sexual  excitement  they  are  absent  from  the  vesicles  of  rodents;  this  and 
other  facts  indicate  that  the  function  of  the  organ  is  primarily  glandular. 
The  lumens  of  the  various  sexual  glands  are  generally  of  very  large  caliber, 
associated  with  the  storing  of  secretions.  Pigment  granules  in  varying 


-ep. 
-t.p. 


FIG.  344. — SEMINAL  VESICLE  AND  DUCTUS  DEF- 
ERENS.  (This  is  natural  size.)  (After  Eberth.) 

ad.,  Adventitia;  am.,  ampulla;  d.,  diverticulum; 
d.  d.,  ductus  deferens;  d.  e.,  ductus  ejacula- 
torius;  m.,  muscularis;  s.  v.,  seminal  vesicle; 
t.  p.,  tunica  propria. 


FIG.  345. — VERTICAL  SECTION  OF  THE  WALL  OF  A 

SEMINAL  VESICLE.     (After  K611iker.) 
ep.,    Simple    epithelium;    g.,    gland-like   depres- 
sion; m.,  muscularis;  t.  p.,  tunica  propria. 


quantity  occur  in  the  epithelial  cells  and  in  the  underlying  connective 
tissue.     They  may  impart  a  brownish  color  to  the  secretion. 

The  ductus  ejaculatorii,  along  their  dorso-median  sides,  are  beset  with  a 
series  of  appendages,  which  do  not  project  externally  but  are  wholly  en- 
closed in  the  connective  tissue  wall  of  the  duct.  Some  of  these  append- 
ages show  the  same  structure  as  the  seminal  vesicles  and  therefore  might 
be  described  as  accessory  seminal  vesicles;  others  are  simply  convolu- 
tions of  alveolo-tubular  glands  which  may  be  compared  with  prostate 
glands.  The  mucous  membrane  of  the  ductus  ejaculatorii  is  like  that  of 
the  seminal  vesicles,  except  that  its  folds  are  not  so  complicated.  Muscle 


344 


HISTOLOGY 


fibers  occur  only  around  the  appendages.  The  wall  of  the  duct  itself  con- 
sists of  an  inner  dense  layer  of  connective  tissue  with  circular  strands,  and 
an  outer  loose  layer  (adventitia)  . 

APPENDICES  AND  PARADIDYMIS. 

The  appendices  are  frequently  called  hydatids,  which  is  a  general  term  for  watery 
cysts.  The  appendix  testis  is  a  small  lobule  of  connective  tissue  projecting  from  the 
groove  between  the  head  of  the  epididymis  and  the  testis  (Fig.  346).  It  is  quite 
constant,  having  been  reported  in  90%  of  the  testes  examined.  The  projection 
is  covered  with  the  peritoneum  of  the  tunica  vaginalis,  which  may  be  thickened  around 
it,  or  corrugated,  suggesting  the  fimbriated  orifice  of  the  uterine  tube.  The  appendix 
consists  of  vascular  connective  tissue  and  encloses  a  canal,  or  fragments  of  canals, 
lined  with  simple  columnar  epithelium  which  is  sometimes  ciliated.  It  is  generally 
not  cystic,  and  it  may  be  pedunculated,  so  that  the  terms  "hydatid  of  Morgagni" 
and  "sessile  hydatid,"  formerly  applied  to  it,  are  inappropri- 
ate. Although  its  canal  has  been  reported  as  connecting 
with  the  seminal  ducts,  this  is  not  now  believed  to  be  the 
case;  the  structure  is  regarded  as  the  degenerated  end  of  the 
Miillerian  duct. 

The  appendix  epididymidis  (stalked  hydatid)  is  not  always 
present.  Among  105  cases  examined  by  Toldt  it  was  found 
l._tv;  twenty-  nine  times.  It  consists  of  loose  vascular  connective 
tissue  covered  by  the  vaginalis,  and  contains  a  dilated  canal 
lined  with  columnar  epithelium,  sometimes  ciliated.  The 
canal  generally  has  no  connection  with  the  tubules  of  the 

FIG.346.-FRONTVIEWOF     epididymis.      It  is  regarded  as  a  persistence  of  detached 
A  TESTIS,  somewhat  re-     degenerating  Wolfnan  tubules,  or  possibly  of  the  terminal 

duced.    (AfterEberth.)  6  .  \      ___ 

e.,  Appendix  epididymi-     portion  of  the  Wolffian  duct. 

The    P^adidymis,    according    to    Toldt    (Verb.    Anat. 


didymidis;  t,  testis;  t.      Gesellsch.,  1802,  pp.  241-242),  occurs  in  two  forms.     The 

v.,  tunica  vaginalis. 

first  is  found  frequently,  but  by  no  means  regularly,  in 

older  embryos  and  in  children.  It  is  a  round  or  elongated  structure,  conspicuous 
because  of  its  white  color,  found  on  the  ventral  side  of  the  spermatic  cord,  either  behind 
the  head  of  the  epididymis  or  higher  up.  Microscopically  it  is  seen  to  be  a  thin,  coiled, 
blind  canal,  expanded  in  places,  and  lined  with  a  simple  columnar  epithelium.  Occa- 
sionally there  are  two  to  four  such  structures  at  varying  distances  from  one  another. 
In  later  years  they  all  disappear.  They  never  contain  spermatozoa. 

The  second  form  of  paradidymis  was  found  by  Toldt  in  late  childhood  and  in  adults, 
but  it  does  not  occur  regularly.  It  is  always  immediately  behind  the  head  of  the 
epididymis  and  in  front  of  the  pampiniform  plexus.  It  consists  of  a  canal,  sometimes 
with  saccular  dilatations,  which  is  easily  followed  with  the  naked  eye.  The  tubule 
may  be  closed  at  both  ends,  or  one  end  may  connect  with  the  epididymis  or  testis; 
sometimes  one  end  connects  with  the  testis  and  the  other  with  the  epididymis.  These 
tubules  may  contain  spermatozoa,  and  they  have  been  said  to  resemble  the  efferent 
ducts  in  structure.  They  may  be  ciliated. 

Toldt  regards  the  first  form  of  paradidymis  as  due  to  persistent  Wolfnan  tubules, 
and  the  second  as  a  late  separation  of  an  efferent  duct  from  Its  connection  with  the 
epididymis.  He  notes  that  the  second  form  may  give  rise  to  cysts  of  varying  size. 
Other  cysts  in  the  vicinity  of  the  epididymis  are  said  to  arise  from  inpocketings  of  the 
tunica  vaginalis. 


PROSTATE 


345 


Smooth 
muscle. 


Glands. 


PROSTATE. 

The  prostate  is  a  group  of  branched  tubulo- alveolar  glands,  imbedded 
in  a  mass  of  muscular  tissue,  which  stands  before  the  outlet  of  the  bladder. 
The  smooth  muscle  of  the  adult  prostate  forms  a  quarter  of  the  bulk 
of  the  organ,  and  together  with  an  elastic  connective  tissue,  it  unites  the 
numerous  glands  in  a  compact  mass.  The  development  of  these  glands 
up  to  the  time  of  birth,  has  been  studied  by  Lowsley  (Amer.  Journ.  Anat., 
1912,  vol.  13,  pp.  299-349).  He  finds  that  the  prostate  includes  from 
fifty-three  to  seventy-four  separate  glands  (the  average  number  being 
sixty-three)  which  are  grouped  in  five 
lobes.  The  middle  lobe  consists  of  nine 
to  ten  large  glands  growing  out  from  the 
dorsal  side  of  the  urethra,  between  the 
bladder  and  the  openings  of  the  ejacu- 
latory  ducts.  The  glands  of  the  posterior 
lobe  grow  out  from  the  dorsal  wall  of  the 
urethra  below  the  ejaculatory  ducts; 
those  of  the  right  and  left  lobes  develop 
from  the  sides  of  the  prostatic  urethra; 
and  those  of  the  anterior  lobe  proceed 
from  its  ventral  surface.  The  anterior 
lobe  is  well  developed  in  young  embryos, 
but  it  "  shrinks  into  insignificance  at  the 
twenty-second  week."  It  may  persist  in 
the  adult,  but  the  great  mass  of  the  pros- 
tatic glands  is  at  the  sides  and  back  of 
the  prostatic  urethra.  The  number  of 
glands  apparently  becomes  reduced.  In 
the  adult  it  is  said  to  be  from  thirty  to 
fifty. 

The  glandular  epithelium  is  simple 
and  either  cuboidal  or  columnar.  It  may  appear  stratified  as  it  passes 
over  the  folds  in  the  walls  of  the  tubules.  Near  the  outlet  of  the  larger 
ducts  the  epithelium  is  like  that  of  the  bladder  and  prostatic  urethra.  In 
the  prostatic  alveoli,  of  older  persons  especially,  round  or  oval  colloid 
masses  from  0.3  to  i.o  mm.  in  diameter  occur;  as  seen  in  sections  (Fig. 
348)  they  exhibit  concentric  layers.  Their  reactions  on  treatment  with 
iodine  solutions  suggest  amyloid.  These  concretions  are  probably  de- 
posited around  fragments  of  cells.  Octahedral  crystals  also  occur  in  the 
prostatic  secretion,  which  is  a  thin  milky  emulsion,  faintly  acid;  it  has  a 
characteristic  odor,  whereas  the  other  constituents  of  the  seminal  fluid  are 
said  to  be  odorless. 


FIG.  347. — FROM  A  SECTION  OF  THE  PROS- 
TATE OF  A  MAN  TWENTY-THREE  YEARS 
OLD.  X  so. 


346 


HISTOLOGY 


The  smooth  muscle  fibers  are  found  everywhere  between  the  pros- 
tatic  lobules;  toward  the  urethra  they  thicken  to  form  the  internal  sphinc- 
ter of  the  bladder.  Smooth  muscle  is  also  abundant  on  the  surface  of 
the  prostate,  and  it  borders  upon  the  striated  fibers  of  the  sphincter  of  the 
membranous  urethra.  The  prostate  is  abundantly  supplied  with  blood 
and  lymphatic  vessels.  The  numerous  nerves  form  ganglionated  plexuses 
from  which  non-medullated  fibers  pass  to  the  smooth  muscles;  others 
of  the  nerves  have  free  endings;  still  others,  both  in  the  outer  and  inner 


Connective  tissue 


Epithelium 


Red  corpuscles  in  a 
blood  vessel. 


S\ 

Smooth 
muscle  fibers. 


FIG.  348. — FROM  A  SECTION  OF  THE  PROSTATE  OF  A  MAN  TWENTY-THREE  YEARS  OLD.     X  360. 
The  epithelium  is  cut  obliquely  at  x,  and  has  artificially  separated  from  the  connective  tissue  at  xx. 

parts  of  the  gland  in  dogs  and  cats,  end  in  cylindrical  lamellar  corpuscles. 
The  utriculus  prostaticus  (uterus  masculinus,  vagina  masculina)  is  a 
small  pocket  lined  with  stratified  epithelium,  opening  into  the  dorsal  wall 
of  the  urethra  midway  between  the  orifices  of  the  ejaculatory  ducts,  or  a 
little  below  them.  It  is  sometimes  absent,  and  is  occasionally  quite  deep. 
Lowsley  failed  to  find  any  small  prostatic  tubules  opening  into  it,  such 
as  have  been  reported  as  occasionally  present.  The  utriculus  prostaticus 
is  the  lower  end  of  the  Miillerian  ducts,  which  have  fused,  and  it  corres- 
ponds with  the  vagina  in  the  female. 

URETHRA  AND  PENIS. 

The  form  of  epithelium  found  in  the  bladder  extends  through  the 
prostatic  to  the  membranous  part  of  the  urethra.     Its  outer  cells  gradu- 


URETHRA 


347 


ally  become  elongated  and  it  changes  to  the  simple  or  few-layered  col- 
umnar epithelium  of  the  cavernous  portion.  In  the  dilatation  of  the  ure- 
thra near  its  distal  end,  the  fossa  navicularis,  the  epithelium  becomes 
stratified  with  its  outer  cells  squamous;  the  underlying  papillae  of  the 
tunica  propria  become  prominent,  and  the  whole  is  the  beginning  of  the 
gradual  transition  from  mucous  membrane  to  skin. 

Glands.  Small  groups  of  mucous  cells  are  scattered  along  the  urethra, 
and  in  the  cavernous  part,  especially  on  the  upper  wall,  they  form  pockets 
called  urethral  glands  (of  Littre).  Often  these  pockets  are  on  the  sides 
of  epithelial  pits  so  that  the  glands  are  branched.  Non-glandular  pits 

Mucous  membrane  of  the  urethra. 


Epithelium.     Tunica  propria.        Urethral  glands.     Submucosa. 


Tunica 
albugineg 


Bundle  of  smooth 
muscle. 


Venous  spaces. 
FIG.  349. — TRANSVERSE  SECTION  OF  THE  PARS  CAVERNOSA  URTHRE..B  OF  MAN.     X  28. 


Connective  tissue 
trabeculse. 


also  occur,  known  as  urethral  lacuna,  and  the  " paraurethral  ducts"  near 
the  external  orifice  are  large  lacunae  of  various  sorts. 

Two  glands  of  considerable  importance  empty  by  irregularly  dilated 
ducts,  ij  in.  long,  into  the  beginning  of  the  cavernous  urethra.  The 
bodies  of  these  bulbo-urethral  glands  (Cowper's  glands)  are  found  one  on 
either  side  of  the  membranous  urethra,  in  close  relation  with  striated 
and  smooth  muscle  fibers.  The  end  pieces,  which  are  partly  alveolar  and 
partly  tubular,  anastomose.  They  consist  of  mucous  cells,  with  inter- 
cellular secretory  capillaries,  and  produce  a  clear,  glairy  mucus,  discharged 
during  sexual  excitement.  The  ducts,  surrounded  by  thin  rings  of  smooth 


348  HISTOLOGY 

muscles,  consist  of  simple  low  epithelium.     They  may  connect  directly 
with  the  end  pieces,  or  a  secretory  duct  may  intervene. 

The  muscularis  of  the  prostatic  part  of  the  urethra  consist  of  an 
inner  longitudinal  and  an  outer  circular  layer  of  smooth  muscles.  Both 
layers  continue  throughout  the  membranous  part;  the  circular  layer  ends 
in  the  beginning  of  the  cavernous  urethra  leaving  only  oblique  and  lon- 
gitudinal bundles  in  its  distal  part. 

Corpus  cavernosum  urethra.  In  the  submucosa  of  the  cavernous 
urethra  there  are  many  veins  (Fig.  349)  which  become  larger  and  more 
numerous  in  and  beyond  the  muscularis.  This  vascular  tissue  which 
surrounds  the  urethra  is  limited  by  a  dense  elastic  connective  tissue  layer, 
the  tunica  albuginea,  and  the  structure  which  is  thus  bounded  is  the  corpus 
cavernosum  urethras.  Toward  the  perineum  it  ends 
in  a  round  enlargement,  the  bulbus  urethras,  and 
distally  it  terminates  in  the  glans  penis.  The  urethra 
enters  the  upper  surface  of  this  corpus  cavernosum 
near  the  bulbus.  Branches  of  the  internal  pudendal 
(pudic)  artery,  namely,  the  arteriae  bulbi  and  the 
urethral  arteries,  penetrate  the  albuginea,  and  the 
former  pass  the  length  of  the  cavernous  body  and 
FIG.  350,-CRoss  SECTION  end  in  the  glans-  These  arteries  have  particularly 
thick  walls  of  circular  muscle,  and  in  cross  sections 
the  mitma  may  be  seen  to  form  coarse  rounded  pro- 
Elasti(CAftirSEbeerthS.)ain'  jections  into  the  lumen.  These  projections  contain 
longitudinal  muscles  and  subdivisions  of  the  inner 
circular  elastic  membrane  (Fig.  350).  The  arteries  in  the  corpus  caver- 
nosum produce  capillaries  found  chiefly  toward  the  albuginea.  The 
capillaries  empty  into  thin-walled  venous  spaces  which  appear  as  endothe- 
lium-lined  clefts  in  a  connective  tissue  containing  many  smooth  muscle 
fibers.  The  cavernous  body  is  permeated  with  these  spaces  which,  at 
times  of  sexual  excitement,  become  distended  with  blood,  reducing  the 
tissue  between  them  to  thin  trabeculae.  Such  distensible  vascular 
tissue  is  known  as  erectile  tissue.  Some  arteries  connect  directly  with  the 
venous  spaces,  and  such  as  appear  coiled  or  C-shaped  in  a  collapsed 
condition  are  called  arteries  helicincs.  The  vence  cavernoscs  have  such  very 
thick  walls  that  they  resemble  arteries.  They  contain  an  abundance 
of  inner  longitudinal  muscle  fibers,  and  since  these  are  not  evenly  dis- 
tributed but  occur  in  columns,  the  lumen  of  the  veins  is  usually  crescentic 
or  stellate  in  cross  section.  Emissary  veins  pass  out  through  the  albu- 
ginea and  empty  into  the  median  dorsal  vein  of  the  penis. 

The  corpora  cavernosa  penis  are  a  pair  of  structures  similar  to  the 
cavernous  body  of  the  urethra,  and  are  found  side  by  side  above  it  (Fig. 
351).  The  septum  between  them  is  perforated  distally  so  that  they 


PENIS  349 

communicate  with  one  another.  Each  is  surrounded  by  a  very  dense 
albuginea,  i  mm.  thick,  divisible  into  an  outer  longitudinal  and  an  inner 
circular  layer  of  fibrous  tissue.  The  septum  is  formed  by  the  median 
fusion  of  these  layers.  The  cavernous  or  erectile  tissue  of  which  these 
corpora  are  composed  is  essentially  like  d 

that  around  the  urethra.  [ 

All  three  cavernous  bodies  are  sur-  _s^^W~~^ 

rounded  by  fascia  and  subcutaneous 
tissue  containing  blood  vessels,  lym- 
phatics and  nerves.  The  lymphatic 
vessels  form  a  superficial  and  a  deep 
set,  the  latter  receiving  branches  from 
the  urethra.  The  principal  sensory 
nerves  are  the  medullated  dorsal  nerves 

of  the  penis.     They  terminate  in  many  '^^ — ~~~^  g 

tactile  corpuscles  in  the  papillae  beneath        FIG.  351-— CROSS  SECTION  OF  A  PENIS. 
the  skin,  in  bulbous  and  genital  corpus- 


i        •       .  t        j  ^«  i  nosa  penis;  f.,  urethra;  g.,  corpus   caver- 

cles  in  the  deeper  connective  tissue,  and         nosum  urethra. 


in  lamellar  corpuscles  found  near  or  in 

the  cavernous  bodies.  Free  endings  also  occur.  The  sympathetic  nerves 
are  from  a  continuation  of  the  prostatic  plexus.  They  constitute  the 
cavernous  plexus,  which  includes  the  major  cavernous  nerves  accompanying 
the  dorsal  nerves  of  the  penis,  and  the  minor  cavernous  nerves  which  enter 
the  roots  of  the  corpora  cavernosa  penis.  The  sympathetic  nerves  supply 
the  numerous  smooth  muscles  of  the  trabeculae  and  cavernous  blood 
vessels.  They  are  said  to  be  joined  by  fibers  from  the  lower  spinal  nerves, 
the  nervi  erigentes. 

FEMALE  GENITAL  ORGANS. 

DEVELOPMENT  AND  GENERAL  FEATURES., 

Although  it  is  probable  that  sex  is  determined  at  the  time  of  the  fer- 
tilization of  the  ovum,  and  that  it  cannot  be  modified  by  subsequent  con- 
ditions of  any  sort,  the  sex  of  young  embryos  cannot  be  recognized.  All 
human  embryos  of  13  mm.  possess  a  prominent  genital  papilla;  they  have 
both  Wolffian  and  Mullerian  ducts,  in  so  far  as  the  latter  have  developed; 
and  they  contain  genital  ridges  which  are  still  in  an  "indifferent  stage"  — 
it  cannot  be  said  whether  they  will  become  ovaries  or  testes  —  (cf.  Fig. 
326,  p.  328).  In  the  female  the  Mullerian  ducts  become  highly  developed, 
the  Wolffian  ducts  degenerate,  and  the  genital  ridges  produce  ovaries. 

The  Mullerian  Ducts.  Before  reaching  the  urogenital  sinus,  the  lower 
ends  of  the  Mullerian  ducts  are  in  contact,  being  situated  between  the 
Wolffian  ducts  (Fig.  352).  The  figure  here  reproduced  represents  a  por- 


350 


HISTOLOGY 


W.d. 


M.d. 


Wd. 


tion  of  the  genital  apparatus  shown  in  Fig.  306,  B,  p.  311,  both  being 
sketched  from  the  beautiful  lithographs  accompanying  Keibel's  funda- 
mental account  of  the  development  of  the  human  urogenital  tract,  which 
students  should  consult  in  its  original  form  (Arch.  f.  Anat.  u.  Entw.,  1896, 
pp.  55-156).  A  fusion  of  the  Miillerian  ducts  begins  just  above  their 
lower  termination  and  extends  downward  to  the  urogenital  sinus.  Thus 
the  entire  ducts  form  a  Y-shaped  structure,  and  the  lower  part  of  the  stem 
becomes  the  vagina.  It  is  at  first  a  solid  cord  of  cells,  but  those  in  the 
center  break  down  and  a  lumen  appears,  "first  in  embryos  of  150-200 
mm."  The  lower  end  of  the  vagina  remains 
closed  by  epithelium  for  some  time  longer,  and  as 
the  vagina  enlarges,  a  transverse  fold,  the  hymen,  is 
formed  at  this  point.  With  the  breaking  down  of 
the  central  cells,  the  hymen  becomes  perforate;  it 
then  usually  forms  a  crescentic  fold  on  the  dorsal 
side  of  the  entrance  to  the  vagina  (Fig.  353).  Its 
remains  permanently  mark  the  orifice  of  the  Miil~ 
lerian  ducts. 

Above  the  vagina  the  Miillerian  ducts  form 
the  lining  of  the  uterus,  which  develops  from  the 
upper  part  of  the  stem  of  the  Y,  and  from  the 
inner  ends  of  its  arms.  This  region  of  junction 
becomes  surrounded  by  a  very  thick  layer  of 
smooth  muscle.  The  occasional  occurrence  of  a 
median  septum  in  the  uterus  or  vagina,  dividing 
them  into  right  and  left  halves,  is  due  to  imperfect  fusion  of  the  Miillerian 
ducts. 

The  outer  portions  of  the  Miillerian  ducts  retain  relatively  thin  walls 
and  become  the  uterine  (or  Fallopian)  tubes.  Each  opens  freely  through 
its  fimbriated  extremity  into  the  abdominal  cavity. 

The  Wolffian  Bodies  and  Wolffian  Ducts.  In  the  female  these  struc- 
tures become  functionless  and  degenerate.  Their  principal  derivative 
is  a  group  of  blind  tubules,  which  may  readily  be  seen  in  the  translucent 
mesentery-like  membrane  extending  between  the  ovary  and  tube.  These 
tubules  were  named  the  "organ  of  Rosenmiiller"  after  their  discoverer, 
who  described  them  in  1802,  and  were  called  the  "parovarium"  (later 
corrected  to  paroophoron)  because  of  their  position  beside  the  ovary; 
but  when  it  was  shown  that  these  tubules  were  homologous  with  the 
epididymis,  they  were  given  a  corresponding  name,  and  are  now  known 
as  the  epobphoron  (««,  upon;  wo^o/oo?,  ovary).  The  epoophoron  consists 
of  "8  to  2o"  transverse  ducts,  which  begin  with  blind  ends  in  or  near  the 
upper  end  of  the  ovary  and  follow  a  more  or  less  convoluted  course  to  the 
longitudinal  duct,  into  which  they  empty  (Fig.  353).  They  are  lined  with 


FIG.  352. — RECONSTRUCTION 
SHOWING  THE  FUSION  OF 
THE  MCLLERIAN  DUCTS. 
(After  Keibel.) 

bl.,  Bladder;  M.d.,  Mullerian 
duct;  u.,  ureter;  ur.,  ure- 
thra; u.s.,  urogenital 
sinus;  W.d.,  Wolffian  duct. 


FEMALE    GENITAL    ORGANS 


351 


uterine  tube 


epo'dpkoron 


paroophoron 


appendix 
vesiculosa 

ovary 


simple  cuboidal  or  columnar  epithelium,  sometimes  ciliated,  and  are 
surrounded  with  muscle  fibers.  Occasionally  there  are  detached  solid 
cords  in  their  vicinity,  and  sometimes  the  tubes  become  cystic.  Obviously 
they  correspond  with  the  efferent  ducts  of  the  testis,  and  the  longitudinal 
duct,  into  which  they  empty,  represents  the  duct  of  the  epididymis.  Some 
of  the  transverse  tubules,  or  the  main  duct  itself,  may  extend  into  soft 
round  nodules  of  tissue  projecting  from  the  mesentery,  to  which  they  may 
be  attached  by  slender  pedicles.  These  appendices  vesiculosa  correspond 
with  the  appendix  of  the  epi- 
didymis. Frequently  there 
is  a  vesicular  appendix  en- 
tirely separate  from  the 
epoophoron,  situated  near  the 
fimbriated  orifice  of  the  uter- 
ine tube,  and  said  by  Felix 
to  develop  around  an  acces- 
sory Mullerian  duct.  Al- 
though accessory  ducts  have 
not  been  found  in  the  male, 
the  relations  of  this  structure 
to  the  Mullerian  duct  suggest 
a  comparison  with  the  ap- 
pendix testis.  Both  in  the 

female   and   the   male   the  >r^  ^M^^~lnaJ°r  mstiimiar  gland 

appendages  have  been  de- 
scribed as  of  two  sorts,  con- 
nected with  the  Mullerian  and 
Wolffian  ducts  respectively. 


clitoris 


ureter 


'  vestibule 
FIG.  353. — DIAGRAM  OF  THE  FEMALE  GENITAL  ORGANS.*, 

The  paroophoron  is  a  remnant  of  the  Wolffian  tubules  corresponding  with  the 
paradidymis.  It  was  first  described  as  nearer  the  uterus  than  the  epoophoron,  and 
situated  as  in  the  diagram,  Fig.  353.  The  tubules  there  shown,  however,  are  pre- 
sumably a  part  of  the  epoophoron;  the  paroophoron  is  now  said  to  be  on  the  opposite 
side  of  the  ovary  (toward  the  right  of  the  diagram),  in  relation  with  the  ovarian  vessels. 
It  disappears  by  the  fifth  year. 

The  lower  end  of  the  Wolffian  duct,  which  corresponds  with  the  ductus  deferens, 
may  remain  as  the  canal  of  Gartner.  This  canal  terminates  near  the  hymen.  It  may 
extend  upward  beside  the  vagina,  and  be  enclosed  in  the  musculature  of  the  lower  part 
of  the  uterus;  usually  it  is  entirely  obliterated. 

Development  of  the  Ovary.  Like  the  testis,  the  ovary  is  formed  from  the 
middle  portion  of  the  genital  ridge.  The  peritoneum  which  covers  it 
gives  rise  to  the  mass  of  cells  in  its  interior,  and  deep  within,  the  cells 
become  arranged  in  medullary  cords  and  a  rete  ovarii.  These  are  rudimen- 
tary structures.  The  rete  cords  do  not  connect  with  the  Wolffian  tubules. 
They  are  said  to  acquire  lumens  toward  birth,  so  that  they  are  bounded 


352  HISTOLOGY 

by  simple  epithelium;  they  remain  in  the  adult  and  may  become  cystic. 
Sexual  cells  disappear  from  the  cords  in  the  central  part  of  the  ovary, 
which  becomes  filled  with  vascular  connective  tissue  and  forms  the  medulla 
in  the  adult.  The  peripheral  part  of  the  ovary,  or  cortex,  contains  great 
numbers  of  sexual  cells,  which  instead  of  being  lodged  in  tubules  as  in 
the  testis,  are  arranged  in  small  groups  surrounded  by  indifferent  cells. 
The  entire  structures  are  primary  follicles,  and  they  are  imbedded  in  a 
stroma  likewise  derived  from  the  peritoneum.  Felix  considers  that  the 

follicles  develop,  for  the  most  part  at 
least,  directly  from  the  tissue  of  the 
genital  ridge,  and  states  that  tubes  or 
cords  growing  in  from  the  peritoneal 
epithelium,  as  described  by  Pfliiger,  do 
not  exist  in  the  human  ovary.  Gener- 
ally it  has  been  said  that  the  primary 
follicles  arise  by  the  subdivision  of  such 
cords  (Fig.  354). 

Ligaments.     As  the  Miillerian  ducts 
come  together  below,  they  occupy  ridges 

FIG.  354.—  SECTION  OF  THE  OVARY  AT  BIRTH.       COVCred  With  peritoneum.      These  ridgCS 

(Waldeyer.)  ,  r  ....  ,  .    , 

a,  Epithelium;  b,   epithelial   cord;   c,  sexual       COaleSCC  SO  as  tO  form  a  partition  which 


crosses  the  pelvis  from  side  to  side  and 
rises  upward  from  its  floor.  Ventral  to 
the  partition  is  the  bladder,  separated  from  it  by  the  vesico-uterine  pouch; 
dorsal  to  it  is  the  rectum,  separated  by  the  deeper  recto-uterine  pouch; 
and  within  it  are  the  uterus  and  tubes.  In  the  adult  these  folds  of  peri- 
toneum extending  laterally  from  the  uterus  constitute  its  broad  ligaments. 
The  Wolffian  bodies  and  ovaries,  which  at  first  occupy  vertical  ridges  on 
either  side  of  the  root  of  the  mesentery,  appear  to  slip  down  or  descend 
into  the  interior  of  the  broad  ligaments,  from  the  dorsal  surfaces  of  which 
the  ovaries  later  project. 

Above  each  ovary  there  is  a  band  of  fibrous  tissue  which  extends  to 
the  orifice  of  the  tube,  and  running  along  this  band  there  is  a  fimbria  known 
as  the  fimbria  ovarica;  this  arrangement  apparently  serves  to  keep  the 
orifice  of  the  tube  in  close  relation  with  the  ovary.  Below  the  ovary, 
between  the  laminae  of  the  broad  ligament,  a  cord  of  fibrous  tissue 
passes  from  it  to  the  musculature  of  the  uterus,  lying  just  below  the 
uterine  .tubes;  this  is  the  ovarian  ligament.  The  round  ligaments  start 
from  the  uterine  musculature  not  far  from  the  ends  of  the  ovarian 
ligaments.  They  pass  downward,  one  on  either  side  within  the  broad 
ligament,  and  terminate  in  the  folds  which  correspond  with  those  of  the 
scrotum.  The  ovarian  and  round  ligaments  are  believed  to  be  subdivi- 
sions of  a  single  structure  equivalent  to  the  gubernaculum  testis. 


FEMALE    GENITAL    ORGANS  353 

The  External  Genital  Organs.  The  urogenital  sinus,  which  receives  the 
urethra  and  vagina,  becomes  a  shallow  space  called  the  -vestibule  (Fig.  353) . 
The  genital  papilla,  with  the  glans  at  its  apex,  becomes  relatively  shorter  as 
the  female  embryo  develops.  It  forms  the  clitoris,  analogous  with  the 
penis,  and  is  covered  by  the  lesser  genital  folds,  the 
labia  minor  a.  (Compare  Fig.  355  with  Fig.  329,  A, 
page  331.)  The  labia  form  a  prepuce  for  the  clitoris 
but  do  not  unite  beneath  it  to  make  a  raphe;  they 
remain  separate,  as  parts  of  the  lateral  boundaries 
of  the  vestibule.  The  larger  genital  folds,  labia 
majora,  likewise  remain  separate.  They  receive  the 
ends  of  the  round  ligaments  of  the  uterus  which  pass 

.  .  FIG.  355. — DIAGRAM  OF 

into  them  over  the  pubic  bones,  sometimes  accom-         THE  EXTERNAL  GENI- 

"  7          ,  TAL    ORGANS   OF  A 

panied  by  a  prolongation  of  the  peritoneal  cavity         FEMALE  EMBRYO. 

f  .  P  a.,  anus;  g.,  glans  clitori- 

f orming  a  processus  vagmalis.     In  late  stages  of  de-         <*is;  g.  {.,  lesser  genital 

r  °  folds    (labia    minora); 

velopment  the  labia  majora  become  large  enough  to  foil's  aaSTmYjora?-*? 
concealthe  clitoris  and  labia  minora,  which  previously  (vestibule*  i  * a !  sinus 
project  between  them. 

OVARY. 

The  ovary  is  an  oval  body  about  an  inch  and  a  half  long,  covered  by 
a  modified  portion  of  the  peritoneum.  Along  its  hilus  it  is  attached  to  a 
mesentery,  the  mesovarium,  which  is  a  subdivision  of  the  broad  ligament 
of  the  uterus.  The  epithelium  of  the  mesovarium  is  continuous  with  that 
of  the  ovary,  and  its  connective  tissue  joins  the  mass  which  forms  the 
ovarian  medulla.  This  tissue,  rich  in  elastic  fibers  and  containing  strands 
of  smooth  muscle,  surrounds  the  vessels  and  nerves.  The  blood  vessels 
are  abundant,  and  they  pursue  a  very  tortuous  course  both  in  the  meso- 
varium and  within  the  ovary.  This  is  strikingly  shown  in  Clark's  in- 
jections (Johns  Hopkins  Hosp.  Rep.,  1900,  vol.  9).  They  are  derived 
in  part  from  branches  of  the  uterine  vessels,  but  are  chiefly  the  terminations 
of  the  ovarian  artery  and  vein.  Large  stems  traverse  the  medulla  and 
form  capillary  plexuses  around  the  follicles  in  the  cortex.  Thin-walled 
lymphatic  vessels  arise  in  the  cortex  below  the  rather  dense  sub-peritoneal 
layer  (or  tunica  albuginea)  and  pass  out  at  the  hilus.  The  nerves  are 
chiefly  non-medullated  sympathetic  fibers,  derived  from  the  plexus  which 
accompanies  the  ovarian  artery,  and  distributed  to  the  blood  vessels. 
Ganglion  cells  have  been  found  near  the  hilus,  and  a  few  medulla  ted  fibers 
occur.  It  is  said  that  certain  fibers  end  in  contact  with  the  cells  of  the 
follicles. 

The  relation  of  the  cortical  stroma  to  the  looser  tissue  of  the  medulla 
is  so  characteristic  that  sections  of  the  human  ovary  containing  few  ova 


354 


HISTOLOGY 


and  no  active  follicles  may  be  readily  identified.  Usually  a  section  of  the 
ovary  may  be  recognized  as  such  without  magnification,  owing  to  the  pres- 
ence of  the  large  cysts  or  follicles  in  which  the  maturing  ova  are  contained. 
These  extend  from  the  cortex  into  the  medulla,  and  are  numerous  even  in 
childhood  (Fig.  356). 

Growth  of  the  Follicles.  It  is  probable  that  all  the  sexual  cells  which  are 
to  be  produced  in  a  life-time  are  present  in  the  ovaries  at  birth.  At  that 
stage,  at  least,  many  of  those  previously  formed  have  already  degenerated ; 
and  the  ovaries  contain  a  great  excess  of  ova,  all  but  a  few  hundred  of 
which  are  destined  to  atrophy  within  the  limits  of  the  genital  glands.  In 
so  far  as  the  sexual  cells  have  ceased  to  multiply  and  have  entered  upon 
the  growth  period,  they  represent  the  last  generation  of  oogonia,  and  are 
being  transformed  into  primary  oocytes.  During  this  transformation 


7 -— 


FIG.  356. — CROSS  SECTION  OF  THE  OVARY  OF  A  CHILD  EIGHT  YEARS  OLD.     X  10. 

I,  Germinal  epithelium;  2,  tunica  albuginea;  3,  peripheral  zone  with  primary  follicles;  4,  vesicular  follicle; 
5»  stroma  ovarii;  6,  medulla;  7,  8,  peripheral  section  of  vesicular  follicles;  9,  hilus,  containing  large 
veins. 

they  increase  greatly  in  size,  finally  becoming  about  0.3  mm.  in  diameter. 
These  egg  cells  have  already  been  described  in  detail  (p.  29).  They  are 
conspicuous  in  sections  as  large,  round,  deeply  staining  cells,  with  round  or 
oval  vesicular  nuclei,  each  containing  a  prominent  nucleolus.  The  cells 
become  so  large  that  frequently  they  are  cut  into  several  sections,  and 
portions  of  protoplasm  without  nuclei  are  to  be  expected.  The  larger 
oocytes  are  surrounded  by  the  clear,  radially  striated  zona  pellucida  (Fig. 
22,  p.  30);  their  protoplasm  may  contain  the  vitelline  bodies  previously 
described. 

The  follicles  are  composed  of  the  cells  which  surround  the  oocytes. 
After  the  groups  of  egg  cells  and  indifferent  cells  become  subdivided,  each 
oocyte  is  typically  surrounded  by  a  single  layer  of  flat  follicular  cells,  and 
this  primary  follicle  lies  isolated  in  the  stroma  of  the  cortex,  beneath  the 
tunica  albuginea  (Figs.  357  and  358).  As  the  follicle  enlarges,  the  follic- 


OVARY 


355 


ular  cells  become  columnar  and  then  stratified  (Fig.  358).  A  crescentic 
cleft  filled  with  fluid  appears  in  the  midst  of  the  stratified  epithelium  on 
one  side  of  the  follicle,  and  by  the  accumulation  of  fluid,  or  liquor  folliculi, 
this  cleft  becomes  a  spherical  cavity  (Fig.  359).  The  fluid  is  regarded  by 
some  as  a  transudate  from  the  blood  vessels,  which  are  abundant  in  the 
stroma  outside  of  the  follicle.  Others  consider  that  it  is  actively  secreted 
by  the  cells  of  the  follicle, 

Egg  cells  in        Germinal 
Certain    Of     Which     Undergo  an  island.        epithelium.      Egg  cell. 

liquefaction.  Spaces  con- 
taining a  stainable  fluid, 
differing  from  that  in  the 
main  cavity,  may  appear 
in  the  epithelium  (Call- 
Exner  bodies),  around 
which  the  cells  are  radially 

arranged.  By  the  development  of  the  main  cavity,  the  stratified  epi- 
thelium becomes  a  relatively  thin  layer,  the  stratum  granulosum,  which 
decreases  in  width  as  the  follicle  enlarges.  The  oocyte  -is  on  one  side  of 
the  follicle,  contained  in  a  heap  of  cells  known  as  cumulus  ob'phorus  (for- 
merly the  discus  proligerus) .  This  is  connected  with  the  wall  of  the  follicle, 
but  in  certain  sections  it  may  appear  completely  detached  (e.g.,  in  a  sec- 


Egg  cell. 

Nucleolus. 

Nucleus. 

Protoplasm. 


Follicular  cells. 


FIG.  357. — FROM  A  SECTION  OF  THE  OVARY  OF  A  CHILD  FOUR 
WEEKS  OLD.     X  240. 


Germinal 
epithelium. 


Tunica          Primary 
albuginea.     follicle. 


A  degenerating 
follicle. 


Follicular  cells. 


Nucleus. 


Nucleolus.     Protoplasm.     Zona  pellucida. 


FIG.  358.  —  FROM  A  SECTION  OF  A  RABBIT'S  OVARY.     X  240. 

tion  at  right  angles  with  the  plane  of  the  page,  near  the  top  of  the  cumulus 
in  Fig.  359). 

Surrounding  the  follicle,  even^in  early  stages,  there  is  a  connective 
tissue  sheath,  the  theca  folliculi  (Fig.  358).  This  later  becomes  differen- 
tiated into  a  vascular  tunica  interna^suid  a  fibrous  tunica  externa  (Fig.  359). 
The  tunica  interna  contains  many  cells  with  abundant  protoplasm.  It  is 
separated  from  the  epithelium  of  the  follicle  by  a  delicate  membrana 
propria. 


HISTOLOGY 


In  distinction  from  the  solid  primary  follicles,  those  with  cavities  are 
known  as  vesicular  follicles  (Graafian  follicles).  They  increase  in  diameter 
from  0.5  to  12.0  mm.,  and  are  then  ready  to  discharge  the  contained  oocyte. 
Occasionally  a  single  follicle  has  two  oocytes,  and  rarely  more.  Arnold 
(Anat.  Rec.,  1912,  vol.  6,  pp.  413-422)  describes  the  ovaries  of  a  negress, 
in  which  he  found  forty-three  follicles  containing  four  oocytes  or  more, 
including  one  which  contained  eleven.  It  cannot  be  stated  whether  the 
additional  oocytes  develop  by  division  of  the  oogonium  within  a  primary 
follicle,  or  by  the  failure  of  a  group  of  primitive  sexual  cells  to  become 
separated  from  one  another. 


Theca 
folliculi. 


Tunica  externa 


Tunica  interna 


Stratum  granulosum. 


Cumulus  oophorus. 


Egg  cell  with  zona 
pellucida,  nucleus 
and  nucleolus. 


FIG.  359- — SECTION  OF  A  LARGE  VESICULAR  FOLLICLE  OF  A  CHILD  EIGHT  YEARS  OLD. 
The  clear  space  within  the  follicle  contains  thejliquor  folliculi. 


X  90. 


Ovulation  and  the  Corpus  Luteum.  Around  the  mature  vesicular 
follicle,  the  tunica  interna  becomes  very  thick  and  cellular,  forming  eleva- 
tions toward  the  stratum  granulosum.  At  this  stage  the  follicle  is  large, 
being  about  half  an  inch  in  diameter,  and  one  surface  of  it  is  so  close  to  the  i 
ovarial  epithelium  as  to  cause  it  to  bulge  and  then  to  rupture.  Through  the 
opening  thus  made  the  liquor  folliculi  escapes,  together  with  the  oocyte. 
The  latter  is  said  to  become  detached  by  the  formation  of  fluid-filled  spaces 
between  the  cells  of  the  cumulus;  it  generally  carries  with  it  more  or  less 
of  the  innermost  layer  of  the  cumulus,  and  these  cells,  because  of  their 
radial  arrangement,  are  termed  the  corona  radiata.  As  the  oocyte  leaves 
the  follicle  there  is  apparently  a  chance  for  it  to  become  lost  in  the  abdom- 
inal cavity,  but  the  fimbriated  orifice  of  the  tube  is  near  at  hand,  and  the 
stroke  of  its  cilia  produces  a  current  toward  its  entrance.  In  a  guinea-pig 


OVARY 


357 


Hensen  observed  that  the  fimbriae  were  in  very  active  motion,  sweeping 
here  and  there  over  the  surface  of  the  ovary  so  powerfully  that  the  effect 
of  ciliary  action  must  have  been  trivial.  The  ova,  surrounded  by  the 
mucoid  cells  of  the  follicles,  adhered  more  closely  to  the  fimbriae  than  to 
the  smooth  surface  of  the  ovary.  Except  toward  the  time  of  ovulation, 
Hensen  found  that  the  fimbriae  were  rela- 
tively inactive  (Zeitschr.  f.  Anat.  u.  Entw., 
1875,  pp.  213-270).  The  discharge  of  the 
>vum  from  the  follicle  is  known  as  ovulation. 
It  may  be  noted  that  in  approaching  the 
peritoneal  epithelium,  through  which  the 
rupture  occurs,  the  follicle  must  push  aside 
or  distend  the  connective  tissue  of  the  tunica 
albuginea.  This  is  ordinarily  a  rather  weak 
layer,  but  it  has  been  suggested  (by  Rey- 
nolds) that  in  some  cases  it  is  more  highly 
developed  and  acts  as  an  obstruction  to  ovulation. 

After  ovulation,  blood  escapes  from  the  capillaries  of  the  tunica  interna 
and  forms  a  clot  within  the  empty  follicle  (Fig.  360).  This  clot  is  some- 
times called  the  corpus  hcemorrhagicum.  On  all  sides  it  is  surroundedfby 
the  cells  of  the  stratum  granulosum,  which  enlarge  and  produce  a  yellow 
fatty  pigment.  They  form  a  yellow  convoluted  zone  which  may  easily 


FIG.  360. — OVARY,  CUT  ACROSS, 
SLIGHTLY  REDUCED. 

a.,  Aperture  through  which  the 
ovum  escaped;  c.  a.,  corpus 
albicans;  cl.,  blood  clot  in  a 
corpus  luteum  of  ovulation; 
th.,  theca  folliculi;  v.  f.,  vesi- 
cular follicle.  (After  Rieffel.) 


Connective  tissue  septa. 


Fibrous  connective  tissue. 


Lutein  cells. 


•>  A  B 

FIG.  361. — A,  PORTION  OF  A  CORPUS  LUTEUM  OF  A  RABBIT.     B,  PORTION  OF  A  CORPUS  LUTEUM  OF  A 

CAT.     X  260. 

In  B  the  luteirK 'cells  have  become  fatty  and  contain  large  and  small  vacuoles. 

be  seen  without  magnification;  the  entire  structure  is  then  known  as  the 
corpus  luteum.  Vascular  strands  of  connective  tissue  extend  between  the 
lutein  cells  (Fig.  361)  and  enter  the  central  clot.  The  extravasated  blood 
breaks  down  into  granules  and  haematoidin  crystals,  and  is  gradually 


358  HISTOLOGY 

absorbed.  It  is  replaced  by  gelatinous  connective  tissue  which  finally, 
contracts  into  a  dense  white  fibrous  nodule,  and  this  scar  is  known  as  the 
corpus  albicans.  Meanwhile  the  lutein  cells  undergo  hyaline  degeneration 
and  become  resorbed.  The  surface  of  the  ovary,  which  is  smooth  in  child- 
hood, becomes  pitted  and  irregular  with  the  increasing  formation  of  these 
corpora  albicantia. 

Provided  that  pregnancy  does  not  take  place,  the  corpus  luteum  reaches 
its  maximum  development  in  about  two  weeks  after  ovulation,  and  it  be- 
comes reduced  to  a  scar  in  about  two  months.  If  pregnancy  occurs,  it 
enlarges  further  and  persists  at  the  height  of  its  development  until  the 
fifth  or  sixth  month.  Its  diameter  is  then  1.5-3.0  cm.,  and  at  the  end  of 
pregnancy  it  is  still  quite  large  and  yellow.  If  the  corpus  luteum  is  re- 
moved, the  ovum  fails  to  become  attached  to  the  wall  of  the  uterus.  There 
is  both  experimental  and  histological  evidence  that  it  produces  an  internal 
secretion  which  is  probably  received  by  the  blood  vessels  invading  it  from 
the  theca.  In  order  to  distinguish  between  the  corpus  luteum  of  pregnancy 
and  that  of  unproductive  ovulation,  the  former  is  called  the  true  corpus 
luteum;  the  latter  is  the  corpus  luteum  spurium. 

Many  follicles  degenerate  at  various  stages  in  their  evolution  without 
discharging  their  ova.  Leucocytes  and  cells  from  the  stratum  granu- 
losum  are  said  to  invade  the  protoplasm  of  the  oocytes,  in  which  they  dis- 
integrate. The  zona  pellucida,  which  surrounds  the  oocyte,  may  become 
conspicuously  folded  and  persist  for  some  time  (Fig.  358).  The  basement 
membrane  of  the  stratum  granulosum  may  also  thicken  and  become  con- 
voluted. These  degenerating  or  atretic  follicles  are  finally  reduced  to 
inconspicuous  scars.  After  the  menopause  the  degeneration  of  the  oocytes 
becomes  general. 

Within  the  stroma  of  the  cortex,  interstitial  cells  are  found,  which  re- 
semble lutein  cells  but  are  smaller.  They  have  been  compared  with  the 
interstitial  cells  of  the  testis,  and  are  said  to  contain  secretory  granules. 
Apparently  they  are  derived  from  the  thecas  of  atretic  follicles  (Cohn, 
Arch.  f.  mikr.  Anat.,  1903,  vol.  62,  pp.  745-772;  Allen,  Amer.  Journ.  Anat., 
1904,  vol.  3,  pp.  89-153). 

UTERINE  TUBES. 

Each  uterine  tube  is  about  5  inches  long  and  extends  from  its  orifice 
in  the  abdominal  cavity  to  its  outlet  in  the  uterus.  It  is  divided  into  the 
fimbriated  funnel  or  infundibulum;  the  ampulla  or  distensible  outer  two- 
thirds,  the  lumen  of  which  is  about  a  quarter  of  an  inch  in  diameter;  the 
isthmus  or  narrow  inner  third,  not  sharply  separated  from  the  ampulla; 
and  the  uterine  portion  which  extends  across  the  musculature  of  the  uterus 
to  the  uterine  orifice.  The  wall  of  the  tube  is  composed  of  three  layers,  a 


OVARY 


359 


mucosa,  muscularis,  and  serosa  (in  addition  to  which  a  tela  submucosa  is 
enumerated  in  the  Basle  nomenclature).  The  mucosa  is  thrown  into  thin 
longitudinal  folds,  which  are  low  in 
the  isthmus,  but  tall  and  branched  in 
the  ampulla  (Fig.  362).  Occasion- 
ally the  branches  anastomose,  en- 
closing a  pocket,  but  glands  are 
absent.  The  epithelium  is  chiefly 
simple  columnar,  and  ciliated,  the 
stroke  of  the  cilia  being  toward  the 
uterus;  but  there  are  areas  of  non- 
ciliated  cells  which  are  said  to  produce 
a  mucoid  fluid.  The  two  types  of 
cells  are  connected  by  intermediate 
forms.  Mucous  cells  are  absent. 

The  folds  of  the  mucous  membrane  are  occasionally  indented  or  over- 
hanging, so  that  in  transverse  sections  detached  fragments  may  appear, 
suggestive  of  villi  (Fig.  363) ;  but  the  fact  that  almost  all  of  the  many  pro- 


FIG.  362. — THE  MUCOSA  OF  THE  UTERINE  TUBE. 
A,  Near  ITS  FIMBRIATED  END;  B.,  NEAR  THE 
UTERUS.  (After  Orthmann.) 


Longitudinal  muscles. 


\ 
Blood  vessels. 


\ 

Circular  muscles. 


V 

Mucosa. 
FIG.    363. — CROSS  SECTION,  NEAR  THE  AMPULLA,  OF  A  UTERINE  TUBE  FROM  AN  ADULT  WOMAN. 

jections  connect  with  the  sub  mucous  layers  indicates  that  they  are  elon- 
gated folds.  Each  of  them  contains  a  thin  layer  of  cellular  connective 
tissue,  in  which  there  are  small  arteries  and  veins  running  chiefly  length- 


36° 


HISTOLOGY 


wise  of  the  tube.  Lymphocytes  occur  in  the  meshes  of  the  tissue  and  lym- 
phatic vessels  have  been  reported.  Occasionally  strands  of  smooth  muscle 
fibers  are  found  within  the  folds. 

The  mucous  membrane  rests  directly  upon  the  tunica  muscularis,  and 
Schafer  considers  that  "the  larger  part  of  the  muscular  layer  must  prob- 
ably be  regarded  as  a  much  thickened  muscularis  mucosae."  The  muscle 
coat  consists  of  a  thick  inner  circular  layer  and  a  thin  outer  longitudinal 
layer  of  smooth  muscle  fibers,  but  both  layers  are  resolved  into  coarse 
bundles  by  the  abundance  of  intermuscular  connective  tissue. 

Since  the  uterine  tubes  are  imbedded  in  the  broad  ligaments,  they  are 
not  closely  invested  by  the  peritoneum.  There  is  a  considerable  layer  of 
loose  vascular  connective  tissue  outside  of  the  muscularis,  and  toward  the 
ovary  this  tissue  may  include  sections  of  the  tubules  of  the  epoophoron. 
It  contains  the  branches  of  the  ovarian  and  uterine  blood  vessels  which 
supply  the  tube.  These  are  accompanied  by  lymphatic  vessels  and 
nerves.  The  latter  innervate  the  tubal  musculature  and  the  mucous 
membrane. 


/Tube 


, Fundus 


UTERUS. 

The  uterus  is  a  pyriform,  muscular  organ,  flattened  dor so-ventr ally. 
It  is  about  two  and  a  half  inches  long,  receiving  the  uterine  tubes  at  its 
upper  end  or  fundus,  and  ending  below  in  the  vagina.  It  is  divided  into 
fundus,  corpus  and  cervix.  The  corpus  and  fundus 
together  have  a  triangular  cavity,  •  which  opens 
into  the  canal  of  the  cervix  through  the  internal 
orifice;  the  canal  communicates  with  the  vagina 
through  the  external  orifice  of  the  uterus.  The 
lining  of  the  cervix  presents  a  feather-like  arrange- 
ment of  folds  on  its  dorsal  and  ventral  surfaces; 
these  are  the  plicce  palmata.  The  walls  of  the 
uterus  consist  of  a  mucosa,  muscularis  and  serosa 
(constituting  the  endometrium,  myometrium,  and 
perimetrium,  respectively). 

The  uterus  is  lined  with  simple  columnar  epi- 
thelium, some  areas  of  which  are  ciliated.  The 
cilia  have  been  described  as  difficult  to  preserve,  and  their  absence 
from  certain  cells  has  been  attributed  to  faulty  fixation.  According 
to  Gage  the  uterine  cilia  are  as  readily  preserved  as  those  which  occur 
elsewhere,  and  he  finds  that  only  one  cell  among  fifteen  or  twenty  is  ac- 
tually ciliated.  Mucous  cells  are  absent.  The  epithelium  forms  slender 
tubular  pits,  the  uterine  glands,  but  these  produce  no  definite  secretion. 
They  are  branched  tortuous  tubes  extending  through  the  broad  mucosa 


^-Vagina 

PIG.  364. — THE  DORSAL  HALF 
OF  A  VIRGIN  UTERUS.  Two- 
thirds  natural  size.  (After 
Rieffel). 


UTERUS  361 

(which  is  i  mm.  thick),  and  invading  to  a  slight  extent  the  muscular  tissue 
beneath.  They  have  been  carefully  modelled  by  Hedblom,  whose  studies 
are  not  yet  published;  he  finds  that  occasionally  they  anastomose  with  one 
another,  and  that  in  their  deeper  portion  they  have  long  horizontal 
branches,  at  right  angles  with  the  main  tube.  Sometimes  a  small  group 
of  glands  opens  into  a  single  depression  of  the  surface  epithelium  (Fig.  365). 
In  older  persons  the  glands  degenerate,  losing  their  connections  with  the 
surface  and  becoming  cystic.  Each  gland  is  surrounded  by  a  delicate 
basement  membrane,  and  between  them  there  is  an  abundant  tunica 


—j Epithelium. 


Gland. 


L_  Mucosa. 


FIG.  365. — Mucous  MEMBRANE  OF  THE  RESTING  UTERUS""OF  A  YOUNG  WOMAN.     X  35. 
(After  Bohm  and  von  Davidoff.) 

propria,  containing  many  blood  vessels.  These  form  capillary  networks 
around  the  glands  and  especially  beneath  the  free  surface.  The  propria 
contains  also  many  lymphocytes,  and  its  lymphatic  vessels  form  a  wide- 
meshed  plexus  with  blind  extensions.  These  structures  are  supported  by 
a  reticular  tissue  framework  containing  many  nuclei. 

The  upper  and  larger  part  of  the  cervix  of  the  uterus  is  likewise  lined 
with  simple  columnar  ciliated  epithelium,  but  its  cells  are  taller  than  those 
of  the  corpus  (60  p  as  compared  with  20  /*).  Mucous  cells  occur,  especially 
in  the  outpocketings  of  epithelial  Jpits  which  constitute  the  branched 
cervical  glands.  They  discharge  a  secretion  which  occludes  the  canal  of 
the  cervix  during  pregnancy.  Often  they  produce  macroscopic  retention 
cysts,  named  "ovules  of  Naboth,"  after  the  Leipzig  anatomist  who  first 


362 


HISTOLOGY 


Mucosa. 


Muscularis. 


described  them.  Toward  the  external  orifice  of  the  uterus  the  epithelium 
becomes  stratified  and  squamous,  and  rests  on  connective  tissue  papillae. 
Thus  it  resembles  the  lining  of  the  vagina  of  which  it  is  a  continuation, 
and  after  the  first  child-birth  it  extends  further  up  into  the  cervix  than 
before. 

The  musculature  of  the  uterus  is  a  thick  investment  of  interwoven 
bundles  which  cannot  be  subdivided  into  well-defined  layers  (Fig.  366). 
It  begins  immediately  outside  the  tunica  propria,  and  its  inner  portion 
has  been  regarded  as  "an  immensely  hypertrophied  muscularis  mucosae." 

Further  out  there  is  a  zone 
containing  many  blood 
vessels,  which  according  to 
this  interpretation  marks 
the  position. of  the  submu- 
cosa  (Schaf  er) .  Accord- 
ing  to  Henle  and  Stohr, 
these  vessels  belong  with 
the  middle  of  three  muscle 
layers,  which  is  named, 
therefore,  the  "  stratum 
vasculare."  It  is  the 
thickest  of  the  layers  and 
its  fibers  are  chiefly  circu- 
lar. The  innermost  layer 
or  "  stratum  submucosum" 
(Stohr)  consists  principally 
of  longitudinal  fibers.  The 
outermost  layer  or  "  stra- 
tum supravasculare"  contains  circular  fibers  internally  and  longitudinal 
fibers  externally.  Some  of  the  latter  are  continuous  with  the  longitudi- 
nal fibers  of  the  uterine  tubes;  others  are  said  to  enter  the  round  liga- 
ments, which  contain  also  some  striated  fibers;  and  still  others  spread 
into  the  broad  ligaments. 

In  the  cervix  the  three -strata  of  muscle  fibers  are  found  to  be  very 
distinct — inner  and  outer  longitudinal,  and  middle  circular.  Although 
the  uterus  generally  contains  few  elastic  fibers,  found  only  in  its  peripheral 
layers  and  running  perpendicular  to  the  plane  of  contraction  of  the  muscles, 
elastic  fibers  are  abundant  in  this  position  in  the  lower  segment  of  the 
corpus  and  vaginal  portion  of  the  uterus.  During  the  first  half  of  preg- 
nancy both  elastic  and  muscular  fibers  increase  in  size  and  number; 
in  the  second  half,  the  elastic  fibers  decrease  in  the  musculature,  but 
increase  in  the  perimetrium  (Stohr).  The  way  in  which  the  thick  layer 
of  muscles  in  the  resting  uterus  becomes  arranged  in  the  thin  layer  of 


Serosa. 
FIG.  366. — FROM  A  TRANSVERSE  SECTION  OF  THE  MIDDLE  OF 

THE  UTERUS  OF  A  GIRL  FIFTEEN  YEARS  OLD.     X  10. 

a,  Epithelium;  b,  tunica  propria;  c,  glands;  i,  inner  muscular 

layer;  2,  middle  muscular  layer;  3,  outer  muscular  layer. 


UTERUS  363 

late  pregnancy  is  an  unsolved  problem,  similar  to  that  presented  by  the 
musculature  of  the  bladder  and  intestine  during  distention. 

The  serosa  covering  the  dorsal  and  ventral  surfaces  of  the  uterus  is  in 
part  a  well-defined  layer,  but  it  blends  with  the  connective  tissue  of  the 
broad  ligaments  laterally  and  below;  and  this  tissue,  from  its  position 
beside  the  uterus,  is  known  as  the  "parametrium."  Imbedded  in  the 
parametrium  the  main  trunks  of  the  uterine  vessels  run  along  the  lateral 
margins  of  cervix  and  corpus,  both  artery  and  vein  showing  many  kinks 
and  convolutions.  The  vessels  are  thus  apparently  adapted  to  the  future 
expansion  of  the  uterus,  but  when  it  retracts  after  pregnancy  they  are 
said  to  show  more  pronounced  bendings,  as  if  they  had  been  permanently 
elongated.  The  parametrium  contains  also  numerous  lymphatic  vessels, 
together  with  the  ganglionated  sympathetic  utero-vaginal  plexus.  Nerves 
from  this  plexus  and  from  the  third  and  fourth  sacral  nerves  supply  the 
uterus. 

MENSTRUATION. 

Menstruation  is  the  periodic  degeneration  and  removal  of  the  super- 
ficial part  of  the  mucosa  of  the  uterus,  accompanied  by  haemorrhage  from 
the  vessels  of  the  tunica  propria.  Three  successive  stages  may  be  dis- 
tinguished, namely  (i)  the  stage  of  congestion,  lasting  four  to  five  days;  (2) 
the  stage  of  desquamation  and  hamorrhage,  four  days;  and  (3)  the  stage  of 
regeneration  and  repair,  seven  days.  Thus  the  entire  process  requires 
about  sixteen  days,  and  after  an  interval  of  twelve  days  the  cycle  begins 
anew. 

For  four  or  five  days  before  the  discharge  occurs,  the  thickness  of  the 
mucosa  increases  greatly,  due  to  the  congestion  of  its  vessels  and  the 
proliferation  of  the  reticular  tissue.  The  glands  become  wider,  longer,  and 
more  tortuous,  opening  between  irregular  swellings  of  the  superficial 
epithelium.  Red  corpuscles  pass  out  between  the  endothelial  cells  of  the 
distended  veins  and  capillaries,  and  form  subepithelial  masses.  This 
stage  of  congestion  and  tumefaction  is  followed  by  one  of  haemorrhage  and 
desquamation.  The  epithelium  of  the  surface  and  outermost  parts  of  the 
glands  becomes  reduced  to  granular  debris,  or  it  may  be  detached  in  shreds. 
The  underlying  vessels  rupture  and  add  to  the  blood  which  had  escaped  by 
diapedesis.  In  the  stage  of  regeneration,  the  epithelium  spreads  from  the 
glands  over  the  exposed  reticular  tissue,  the  congestion  diminishes,  and 
the  mucosa  returns  to  its  resting  condition.  The  cervix  takes  no  part  in 
menstruation  except  that  the  secretion  of  its  glands  may  increase  during 
the  stage  of  congestion. 

Beginning  at  puberty  (13-15  years)  menstruation  takes  place  normally 
once  in  28  days  for  33  years,  more  or  less.  During  pregnancy  it  is  interrupted, 


HISTOLOGY 


although  the  time  when  it  should  occur  may  be  indicated  by  slight  uterine  con- 
tractions and  finally  by  those  which  cause  the  delivery  of  the  child.  Thus  the 
duration  of  pregnancy  is  described  as  ten  menstrual  cycles.  The  significance  of  men- 
struation is  suggested  by  conditions  in  those  mammals  in  which  sexual  seasons  are 
annual  or  infrequent.  In  them  a  period  of  congestion,  accompanied  by  uterine  changes 
which  are  sometimes  closely  comparable  with  those  of  menstruation,  precedes  sexual 
intercourse  and  ovulatioli.  Thus  in  the  bitch  ovulation  takes  place  when  the  external 
bleeding  "is  almost  or  quite  over,"  and  this  is  the  time  of  coitus.  Domestication  in 

Disintegrating 
epithelium.      •.v\>iUv,' 

Blood  vessel.- -^^^^j^^fe. Surface  epithelium. 


Disintegrating 
epithelium. 


--  Pit-like  depression. 


—  Bifurcating  tubule. 


..  Coiled  tubule. 


Cystic  tubule 


p 

Blood  vessel.  *-^~ 


— -  Blood:;vessel. 


Muscularis. 


FIG.  367. — Mucous  MEMBRANE  OF  A  VIRGIN  UTERUS  DURING  THE  FIRST  DAY  OF 
MENSTRUATION.     X  30.     (Schaper.) 


various  animals  causes  an  increased  frequency  of  the  congestive  cycles,  sometimes 
unaccompanied  by  ovulation.  It  is  generally  accepted  that  human  menstruation 
may  take  place  without  ovulation,  and  that  ovulation  may  occur  between  menstrual 
periods,  and  also  during  pregnancy.  It  may  even  occur  in  children  before  menstrua- 
tion has  begun.  Nevertheless  ovulation  probably  occurs  usually  and  normally  at  the 
close  of  menstruation.  Coitus  is  not  considered  to  be  a  factor  in  inducing  ovulation, 
but  it  is  said  that  in  the  rabbit  and  ferret,  and  in  pigeons,  ovulation  may  fail  to  occur 
in  the  absence  of  the  male. 


MENSTRUATION  365 

The  following  considerations  are  also  important  in  establishing  the  age  of  young 
embryos.  The  time  required  for  spermatozoa  to  travel  to  the  upper  end  of  the  tube, 
where  fertilization  takes  place,  is  probably  about  twenty-four  hours.  There  they 
may  fertilize  the  ovum  at  once  if  ovulation  has  just  occurred.  They  retain  their 
vitality  and  are  capable  of  fertilizing  the  ovum  during  a  period  of  ten  days  in  the 
rabbit,  and  this  may  be  true  also  of  man.  Thus  it  is  probable  that  if  coitus  has  occurred 
shortly  before  menstruation,  the  spermatozoa  may  remain  active  in  the  tube,  and 
fertilize  the  ovum  discharged  at  the  close  of  the  following  menstruation. 


THE   DISCOVERY   OF   MAMMALIAN   OVA. 

During  the  seventeenth  century  the  ovary  was  called  the  testis  muliebris,  or  testis 
fcemineus.  It  was  believed  to  produce  the  mucoid  secretion  which  escapes  from  the 
genital  orifice,  and  this  was  regarded  as  seminal  fluid.  The  uterine  tubes  were  accord- 
ingly the  vasa  deferentia  mulierum,  serving  to  convey  this  fluid  to  the  uterus,  where, 
through  a  mixture  and  interaction  of  the  male  and  female  semina,  an  embryo  was 
produced.  Aristotle  had  argued  to  the  contrary,  but  his  opinion  was  summarily  dis- 
posed of  by  Bartholin,  who  discussed  the  ovaries  as  follows  (Anatomia,  1666): 

"Their  function  is  to  produce  semen  in  their  own  way,  which  Aristotle,  against  all 
reason  and  observation,  has  dared  to  deny  to  women,  contrary  to  the  express  teaching 
of  Hippocrates. " 

The  ancient  doctrine  of  Aristotle,  expounded  in  his  treatise  on  the  generation  of 
animals,  was  based  upon  the  familiar  facts  that  menstruation  marks  the  beginning, 
and  ceases  at  the  end,  of  the  child-bearing  period;  and  moreover  menstruation  is 
interrupted  while  the  embryo  is  being  formed.  Therefore  he  concluded  that  the  men- 
struum supplies  the  substance  and  material  for  the  new  body,  which  arises  like  the 
curd  in  milk,  through  the  agency  of  the  semen.  The  semen  engenders;  the  menstruum 
nourishes.  The  theory  had  already  been  advanced  that  the  semen  comes  from  all 
parts  of  the  body,  and  that  its  particles  reproduce  the  structures  from  which  they  are 
derived.  This  enticing  speculation,  revived  by  Darwin  in  his  theory  of  pangenesis, 
was  discussed  at  length  and  rejected  by  Aristotle. 

Generation,  therefore,  was  considered  to  result  from  the  mixing  of  two  fluids,  and 
would  have  remained  a  barren  physico-chemical  problem  until  recent  times,  if  further 
morphological  observations  had  not  been  made.  The  view  of  Bartholin  had  at  least 
the  merit  of  definitely  associating  the  ovary  with  the  reproductive  function.  Vesalius 
and  Fallopius  had  seen  the  follicles  and  corpora  lutea;  Fallopius  described  them  as 
"vesicles  filled  with  water  or  aqueous  humor,  some  limpid  and  others  yellow  (Observa- 
tiones,  1588).  Many  others  had  observed  them,  and  from  their  resemblance  to  the 
ova  of  birds  they  had  even  been  called  "ova,"  when  in  1672  a  young  Dutch  physician, 
Regnerus  de  Graaf,  made  his  thorough  study  of  the  female  genital  tract. 

De  Graaf  concluded  that  the  "semen  muliebre"  is  not  produced  by  the  "testes 
muliebres,"  but  that  the  general  function  of  the  latter  is  "to  produce  and  nourish 
ova,  and  bring  them  to  maturity."  Consequently  he  proposed  to  substitute  the  name 
ovary,  and  to  call  the  tubes  oviducts.  He  declared  that  the  ova  escaped  from  the 
follicles  through  minute  apertures  (in  the  rabbit  admitting  a  bristle)  and  made  their 
way  through  the  tubes  to  the  uterus,  in  which  they  developed.  The  abnormal  forma- 
tion of  a  human  embryo  within  the  tube  was  figured  and,  to  a  certain  extent,  explained. 
De  Graaf  studied  many  mammals,  and  especially  rabbits.  He  found  minute  ova  in 
the  oviducts  and  observed  the  follicles  from  which  they  had  escaped.  In  older  stages 
he  recorded  a  general  agreement  between  the  number  of  corpora  lutea  and  embryos. 


366  HISTOLOGY 

Since,  however,  he  frequently  referred  to  the  entire  follicles  as  ova,  his  results  were  not 
promptly  accepted;  the  diameter  of  the  isthmus  of  the  tube  is  so  small  that  the  entrance 
of  the  follicles  into  the  uterus  was  considered  impossible.  It  was  a  matter  of  easy 
observation  to  determine  more  precisely  the  relation  of  the  ova  to  the  follicles.  After 
many  years  this  was  done  by  Von  Baer,  an  eminent  embryologist,  whose  studies 
of  the  chick  are  regarded  as  "the  most  profound,  exhaustive  and  original  contribution 
to  embryology  which  has  ever  been  made"  (Minot).  This  work  bears  the  famous 
subtitle  " Beobachtung  und  Reflexion"* — the  German  expression  of  Haller's  "Observa- 
tions suivies  de  Reflexion"  and  De  Graaf's  "  Cogitationes  atque  observations. "  After 
describing  the  condition  of  the  ova  in  the  tubes  of  the  bitch,  Von  Baer  writes: 

"It  remained  for  me  to  ascertain  the  condition  of  ova  in  the  ovary,  for  it  seemed 
clearer  than  day  that  ova  so  small  as  those  found  in  the  tubes  did  not  represent  Graafian 
follicles  expelled  from  the  ovary;  and  I  did  not  consider  it  probable  that  such  solid  bodies 
had  been  coagulated  from  the  fluid  of  the  vesicles.  Now,  contemplating  the  ovaries 
before  making  an  incision,  I  clearly  distinguished  in  almost  every  vesicle,  a  yellowish- 
white  point  unattached  to  the  walls,  which  swam  about  freely  in  the  fluid  when  the 
vesicle  was  pressed  upon  with  a  probe.  Led  on  by  a  certain  curiosity,  rather  than 
moved  by  hope  that  with  the  naked  eye  I  had  seen  ovules  in  the  ovaries  through  all 
the  coats  of  the  Graafian  follicle,  I  opened  a  vesicle,  and  taking  out  a  point  in  question 
on  the  blade  of  a  knife,  I  placed  it  under  the  microscope.  I  was  overcome  with  amaze- 
ment when  I  saw  the  ovule,  now  recognized  outside  of  the  tubes,  so  clearly  that  a  blind 
man  could  hardly  doubt  it.  Surely  it  is  strange  and  unexpected  that  an  object  so  per- 
sistently sought  for,  and  endlessly  described  as  inextricable,  in  every  physiological 
compendium,  could  so  easily  be  placed  before  the  eyes"  (De  ovi  genesi,  Lipsiae,  1827). 

Thus  the  ova  in  mammalian  ovaries,  which  had  long  been  believed  to  exist,  were 
first  definitely  seen  within  the  follicles  one  hundred  and  fifty  years  after  the  discovery 
of  the  microscopic  spermatozoa,  the  existence  of  which  had  never  been  suspected. 


THE  DECIDUAL  MEMBRANES  OF  THE  UTERUS  AND  EMBRYO. 
DEVELOPMENT  AND  GENERAL  FEATURES. 

Before  describing  the  mucous  membrane  of  the  uterus  during  preg- 
nancy, it  is  necessary  to  consider  the  membranes  which  envelop  the 
embryo.  Although  these-  are  in  contact  with  the  lining  of  the  uterus  and 
in  part  intimately  blended  with  it,  they  are  portions  of  the  embryo  itself. 
The  external  membrane,  toward  the  uterus,  is  known  as  the  chorion;  the 
inner  membrane,  toward  the  embryo,  is  the  amnion.  Since  the  embryo 
receives  its  nutriment  from  the  wall  of  the  uterus  through  blood  vessels 
in  the  chorion,  these  membranes  develop  very  early  and  thus  provide  for 
rapid  growth.  They  are  already  present  in  the  youngest  human  embryos 
which  have  yet  been  obtained. 

Of  the  fertilization  and  segmentation  of  the  human  ovum,  which 
doubtless  take  place  in  the  upper  part  of  the  uterine  tube,  nothing  is 
known  except  by  inference  from  lower  animals.  The  four-celled  stage 
has  been  observed  once  in  a  monkey,  but  the  youngest  known  human 
embryo  is  already  provided  with  ectoderm,  mesoderm  and  entoderm,  and 
has  entered  the  uterus.  As  a  purely  hypothetical  figure,  we  venture  to 


DECIDUAL    MEMBRANES 


367 


present  the  diagram  Fig.  368,  A,  followed  by  the  diagrams  B  and  C  which 
include  many  features  actually  observed. 

In  Fig.  368,  A,  a  mass  of  cells  (ect.)  represents  the  ectoderm  which  will 
later  cover  the  body  and  line  the  inner  membrane  or  amnion.  This  ecto- 
derm probably  arises  in  connection  with  the  layer  (tr.)  which  covers  the 
entire  vesicle  and  becomes  the  epithelium  of  the  outer  membrane  or 
chorion.  The  layer  in  question  has  been  named  the  trophoblast  (or 
trophoderm) . 


am.c 


ect 


cho. 


FIG.    368. — DIAGRAMS  ILLUSTRATING  THE  EARLY  DEVELOPMENT  OF  THE  HUMAN  EMBRYO  (A  is  HYPO- 
THETICAL). 

al.,  Allantois;  am.  c.,   amniotic  cavity;   cho.,   chorion;  coe.,   coelom;  ect.,   ectoderm;    m,    mesoderm;    tr. 
trophoderm  (trophoblast);  x,  entodermal  cyst;  y.  s.,  yolk-sac. 


The  term  trophoblast  (i.e.,  nutritive  layer)  was  introduced  by  Hubrecht  to  corre- 
spond with  the  terms  epiblast,  mesoblast  and  hypoblast,  which  he  used  for  the  other 
germ  layers.  Since  these  are  now  generally  called  ectoderm,  mesoderm  and  entoderm, 
the  outer  layer  should  be  trophoderm,  and  the  substitution  of  this  name  is  therefore 
recommended.  Trophoderm  has,  however,  been  used  by  Minot  for  the  proliferating 
part  of  Hubrecht's  trophoblast.  It  may  be  noted  that  a  similar  difficulty  is  encoun- 
tered in  His's  angioblast  which,  as  a  germ  layer,  should  be  angioderm.  Schafer 
applies  angioblast  logically  to  the  individual  cells  which  become  the  endothelial 
lining  of  vessels.  Consistency  requires  the  use  of  "-derm"  for  germ  layers,  leaving 
"-blast"  for  formative  cells. 

In  addition  to  the  trophoderm  and  ectoderm,  the  hypothetical  stage 
shown  in  Fig.  368,  A,  exhibits  a  yolk-sac  completely  lined  with  entoderm. 
Between  the  trophoderm  and  entoderm,  the  mesoderm  has  appeared  and 
is  separating  into  somatic  and  splanchnic  layers,  with  the  body  cavity 
between  them.  The  somatic  mesoderm  is  closely  applied  to  the  trophoderm, 
and  together  they  form  the  chorion:  the  splanchnic  mesoderm  is  against 
the  entoderm  of  the  yolk-sac,  and  forms  the  outer  layer  of  its  wall.  The 
early  and  rapid  development  of  the  mesoderm  is  characteristic  of  human 
embryos,  as  may  be  inferred  from  the  later  stages. 

In  the  diagram  Fig.  368,  B.  the  amniotic  cavity  has  appeared  in  the  ecto- 
derm. It  is  believed  to  arise  as  a  cleft  in  a  solid  mass  of  cells,  and  not  by 
the  coalescence  of  ectodermal  folds  as  in  the  chick;  however,  in  the  young- 
est human  embryos  observed,  it  is  completely  formed.  The  entoderm 


368  HISTOLOGY 

shows  an  outpocketing  extending  into  the  mesoderm  at  the  future  caudal 
end  of  the  embryo;  this  is  the  allantois,  which  soon  becomes  a  slender  tube 
(Fig.  368,  C).  The  mesoderm  in  which  it  is  lodged  later  produces  the 
"body  stalk." 

The  allantois  develops  very  early  in  human  embryos,  being  present  in  most  if  not 
in  all  of  the  specimens  thus  far  obtained.  Possibly  there  is  no  allantois  in  the  very 
imperfect  embryo  described  by  Bryce  and  Teacher  (Contributions,  etc,  Glasgow, 
1908),  and  there  is  uncertainty  as  to  its  presence  in  Peters's  embryo  (Ueber  die  Einbet- 
tung  des  menschlichen  Eies,  Leipzig,  1899);  but  in  other  very  young  specimens  it  is 
well  denned.  According  to  Keibel,  the  allantois  first  appears  in  chicks  of  about 
twenty  segments;  in  rabbits  of  eleven  segments;  in  pigs  of  four  to  five  segments; 
and  in  the  apes  and  man,  before  any  segments  have  formed.  Its  very  early  appearance 
in  human  embryos  is  probably  correlated  with  the  rapid  establishment  of  the  placental 
circulation,  for  the  umbilical  vessels  are  primarily  the  vessels  of  the  allantois. 

In  Fig.  368,  B  and  C,  the  entoderm  of  the  yolk-sac  is  represented  as  giving  rise  to  a 
detached  cyst  (x).  There  is  a  cyst  of  this  sort  within  the  chorionic  cavity  of  the 
somewhat  damaged  Herzog  embryo  in  the  Harvard  Collection,  and  a  smaller  detached 
cyst  in  the  very  perfect  Minot  embryo.  (These  will  be  further  described  by  the  writer 
in  a  subsequent  publication.)  It  is  possible  that  such  cysts  are  of  regular  occurrence, 
although  destined  to  atrophy.  They  may  be  lodged  in  a  strand  of  mesoderm  extend- 
ing from  the  lower  pole  of  the  yolk-sac  downward  to  the  chorion  (Grosser,  Anat. 
Hefte,  1913,  Abt.  I,  vol.  47,  pp.  653-686),  and  they  may  arise  as  indicated  in  the 
diagrams  (Fig.  368). 

As  the  body  cavity  develops  between  the  somatic  and  splanchnic 
layers  of  mesoderm;  it  is  at  first  bridged  by  strands  of  mesenchymal  tissue, 
forming  the  "magma  reticulare."  These  strands  become  attenuate  and 
break  down,  so  that  the  yolk-sac  is  then  suspended  in  a  well-defined 
"extra-embryonic  ccelom."  This  part  of  the  ccelom,  although  within  the 
embryonic  membranes,  is  outside  of  the  body  proper  of  the  embryo,  as  will 
appear  in  the  following  diagrams. 

The  arrangement  of  the  membranes  surrounding  human  embryos  of 
about  2  mm.  is  shown  in  Fig.  369,  A.  The  chorion  has  become  covered 
with  branching  elevations  or  villi,  which  contain  a  vascular  core  of  chori- 
onic mesoderm,  not  shown  in  the  diagram.  The  body  of  the  embryo  is 
connected  with  the  chorion  by  the  mesodermic  body  stalk  containing  the 
allantois.  This  has  become  relatively  slender.  On  one  side  it  is  covered 
by  the  ectoderm  of  the  amnion.  The  ectoderm,  as  in  preceding  stages, 
may  be  divided  into  two  parts.  Toward  the  yolk-sac  it  is  thickened  and 
there  it  forms  the  axial  medullary  tube  and  gives  rise  ultimately  to  the 
epidermis  covering  the  body.  Continuous  with  this  epidermal  ectoderm 
is  the  thinner  portion  which  lines  the  amnion,  as  shown  in  the  figure. 
The  amnion  forms  a  membranous  sac  attached  to  the  ventral  side  of  the 
embryo,  leaving  an  aperture  through  which  the  yolk-sac  projects  downward 
into  the  extra-embryonic  ccelom.  The  ccelom  now  extends  between  the 
amnion  and  chorion,  except  at  the  narrow  body  stalk.  The  yolk-sac  has 


DECIDUAL    MEMBRANES 


369 


given  rise  to  the  fore-gut  and  hind-gut,  and  the  allantois  now  appears  as 
an  appendage  of  the  latter. 

In  Fig.  369,  B,  the  embryo  is  represented  as  rotated  so  that  its  head  is 
downward  and  its  ventral  side  toward  the  left.  It  is  now  connected  with 
the  membranes  by  an  umbilical  cord,  the  composition  of  which  may  be  seen 
by  comparing  A  and  B.  Its  principal  constituent  is  the  elongated  body 
stalk,  containing  the  allantois  and  covered  above  and  on  the  sides  with 
adherent  amnion.  Below,  the  amnion  also  forms  the  covering  of  the  cord, 
but  here  it  is  separated  from  the  body  stalk  by  an  extension  of  the  body 
cavity.  The  yolk  stalk  passes  from  the  primary  loop  of  intestine  through 
the  cavity  of  the  umbilical  cord  to  the  yolk-sac,  in  which  it  terminates. 


A  B 

FIG.  369. — DIAGRAMS  ILLUSTRATING  THE  DEVELOPMENT  OF  THE  EMBRYONIC  MEMBRANES  AND  THE  FOR- 
MATION OF  THE  UMBILICAL  CORD. 
al.,  Allantois;  am.,  amnion;  am.  c.,  amniotic  cavity;  cho.,  chorion;  coe.,  ccelom;  y.  s.,  yolk-sac. 

This  sac  is  now  lodged  in  its  permanent  position  between  the  amnion  and 
chorion.  Ultimately  the  parts  of  the  allantois,  yolk  stalk  and  body 
cavity  within  the  cord  are  obliterated. 

The  appearance  of  a  human  embryo  at  a  stage  intermediate  between 
those  shown  in  Fig.  369  is  reproduced  in  Fig.  370.  An  irregular  piece  cut 
out  from  the  chorionic  vesicle  forms  the  background  of  the  picture. 
Around  the  cut  edges  of  this  piece  the  shaggy  chorionic  villi  are  seen, 
directed  toward  the  wall  of  the  uterus.  At  the  top  of  the  figure  is  the 
spherical  yolk-sac  lodged  between  chorion  and  amnion,  between  which 
the  yolk  stalk  passes  to  the  distal  end  of  the  umbilical  cord,  which  it  enters. 
The  amnion  is  a  membranous  sac  completely  enclosing  the  embryo;  in 
the  figure,  half  of  it  has  been  cut  away  to  show  the  embryo  within.  The 
skin  of  the  embryo  is  continuous  with  the  covering  of  the  umbilical  cord, 
and  distally  this  covering  is  reflected  and  becomes  continuous  with  the 
amnion. 

In  later  stages  the  umbilical  cord  is  greatly  elongated.  It  contains 
the  umbilical  vessels  which  pass  between  the  embryo  and  the  chorion, 
24 


370 


HISTOLOGY 


through  the  persistent  body  stalk.  The  amniotic  cavity  greatly  enlarges 
to  accommodate  the  growing  embryo,  and  the  mesoderm  of  the  amnion 
comes  in  contact  with  that  of  the  chorion,  to  which  it  adheres  more  or  less 
firmly.  The  embryo  is  bathed  in  the  amniotic  fluid  (liquor  amnii),  of 
uncertain  derivation,  once  thought  to  be  sweat  from  the  embryo,  and  later 
considered  to  contain  the  products  of  the  Wolffian  body,  and  urine  from 
the  permanent  kidneys.  Occasionally  toward  birth  the  meconiunrifrom 


FIG.  370. — A  NORMAL  HUMAN  EMBRYO  OF  10.0  MM.,  REMOVED  SURGICALLY  WITH  THE  UTERUS,  Six  WEEKS 

AFTER  THE  LAST  MENSTRUATION. 

the  intestine  mingles  with  it  and  discolors  it.     It  is  now  generally  believed 
to  be  secreted  by  the  amniotic  epithelium. 

Relation  between  the  Embryonic  Membranes  and  the  Uterus.  When  the 
embryo  within  its  chorionic  vesicle  passes  from  the  tube  into  the  uterus, 
it  is  probably  in  a  stage  comparable  with  that  shown  in  Fig.  368  (B  or  C). 
By  the  activity  of  the  proliferating  trophoderm,  the  uterine  mucosa  is 
partially  destroyed  and  the  chorionic  vesicle  becomes  imbedded  in  its 
substance.  This  process  is  known  as  the  implantation  of  the  ovum.  The 
walls  of  the  vessels  in  the  tunica  propria  of  the  uterus  are  broken  down, 
and  the  maternal  blood  flows  over  and  around  the  chorionic  villi,  in  con- 


DECIDUAL    MEMBRANES 


371 


tact  with  which  it  does  not  clot.  Elsewhere  in  the  body,  except  in  retic- 
ular  tissue,  blood  clots  on  escaping  from  the  endothelial  tubes.  Toward 
the  uterine  cavity,  however,  there  is  a  clot  which  completes  the  encapsula- 
tion of  the  chorionic  vesicle  in  the  mucosa.  The  mucous  membrane  itself 
later  passes  entirely  around  the  vesicle  as  shown  in  Fig.  371,  A. 

The  greater  part  of  the  mucosa  of  the  uterus  becomes  cast  off  at  the  end 
of  pregnancy;  thus  it  forms  a  membrana  decidua,  which  may  be  subdivided 
into  three  parts — (i)  the  decidua  basalis  (or  serotina)  on  which  the  im- 
planted chorionic  vesicle  rests,  and  which  forms  the  maternal  part  of  the 
placenta;  (2)  the  decidua  capsularis  (or  reflexa)  which  spreads  over  the 
part  of  the  vesicle  which  is  toward  the  uterine  cavity;  and  (3)  the  decidua 
vera,  which  lines  the  remainder  of  the  uterus.  These  subdivisions  of  the 
decidua  are  indicated  in  Fig.  371,  A. 


FIG.  371. — THE  UTERUS  AND-DECIDUAL  MEMBRANES  IN  EARLY  PREGNANCY,  A,  AND  IN  LATE  PREGNANCY, 

B.     THE  CORD  HAS  BEEN  CUT  AND  THE  EMBRYO  REMOVED  FROM  B. 
am.,  Amnion;  am.  c.,  amniotic  cavity;  c.,  cervix;  ch.,  chorion;  c.  u.,  cavity  of  the  uterus;  d.  b.,    decidua 

basalis;  d.  c.,  decidua  capsularis;  d.  v.,  decidua  vera;    m.,  amnion  and  chorion  laeve  drawn  as  one 

line;  pi.,  placenta;  u.'c.,  umbilical  cord;  y.  s.,  yolk-sac. 

Soon  after  the  ovum  becomes  implanted,  the  chorion  ceases  to  be 
uniformly  covered  with  villi.  The  villi  toward  the  decidua  basalis  elon- 
gate and  branch  freely,  producing  the  shaggy  chorion  frondosum;  this  is  the 
embryonic  portion  of  the  placenta.  As  the  chorionic  vesicle  enlarges,  the 
villi  directed  away  from  the  wall  of  the  uterus,  toward  the  decidua  cap- 
sularis, become  shorter  and  disappear,  so  that  a  large  portion  of  the 
chorion  becomes  smooth — the  chorion  Iceve.  Usually  the  umbilical  cord 
passes  to  a  nearly  central  position  in  the  chorion  frondosum;  rarely  it  has 
a  "marginal  attachment"  at  the  periphery  of  the  frondosum,  and  it  may 
have  a  "velamentous  insertion"  in  the  adjacent  part  of  the  chorion  laeve, 
through  which  the  umbilical  vessels  then  extend  to  the  frondosum. 

With  the  growth  of  the  embryo,  which  fills  and  distends  the  uterine 
cavity,  the  decidua  capsularis  becomes  thin,  degenerates,  and  is  resorbed, 


372 


HISTOLOGY 


so  that  in  the  last  half  of  pregnancy  the  chorion  laeve  rests  directly  against 
the  decidua  vera  (Fig.  371,  B). 

The  placenta  at  birth  is  a  discoid  mass  of  spongy  vascular  tissue,  about 
7  in.  in  diameter  and  i  in.  thick,  weighing  a  pound.  It  is  composed  of  two 
parts,  the  placenta  uterina  and  placenta  fetalis,  which  in  certain  lower 
mammals  can  be  readily  separated,  but  in  others,  and  in  man,  they  cannot 
be  disengaged.  The  uterine  portion,  as  already  stated,  is  the  decidua 
basalis,  and  the  embryonic  or  fetal  portion  is  the  chorion  frondosum.  At 
the  margin  of  the  placenta,  the  chorion  frondosum  is  continuous  with  the 
chorion  laeve,  which  is  adherent  to  the  decidua  vera.  Lining  the  chorionic 
cavity  and  spreading  from  the  distal  end  of  the  umbilical  cord,  the  amnion 
forms  a  complete  sac,  with  a  smooth  and  glistening  surface  toward  the 
embryo.  It  is  lightly  adherent  to  the  chorion  lasve  and  to  that  surface  of 
the  placenta  which  is  toward  the  embryo.  From  the  way  in  which  the 
chorion  laeve  and  chorion  frondosum  become  differentiated,  the  fact  that 
small  accessory  placentas  sometimes  occur  near  the  main  mass  may  be 
readily  understood;  detached  groups  of  chorionic  villi  continue  their  growth, 
and  their  vessels  communicate  with  those  of  the  adjacent  placenta.  Such 
small  accessory  structures  are  known  as  succenturiate  (i.e.,  recruited) 
placentas. 

Fate  of  the  Membranes  at  Birth.  Shortly  before  birth,  the  cervix  of 
the  uterus  dilates  and  the  sac  of  membranes  containing  the  liquor  amnii 
bulges  into  it.  The  membranes  thus  exposed  are  ruptured,  and  the 
amniotic  fluid  escapes.  The  birth  of  the  child  follows,  and  the  umbilical 
cord  then  extends  from  the  navel  through  the  vagina  to  the  placenta.  The 
cord  is  so  short  in  some  mammals  that  it  ruptures  with  the  expulsion  of 
the  embryo;  in  other  forms  it  is  bitten  off  or  otherwise  severed,  setting  free 
the  embryo.  Occasionally  the  membranes  rupture  in  such  a  way  that  the 
head  of  the  infant  remains  more  or  less  covered  with  a  cap  of  amnion  and 
chorion  laeve,  formerly  known  as  the  "caul."  After  the  birth  of  the  child 
the  uterine  musculature  contracts  quite  rapidly,  and  in  about  half  an  hour 
the  after-birth  is  expelled,  the  sac  of  membranes  being  turned  inside  out 
in  this  process.  The  part  from  the  fundus  of  the  uterus  is  forced  out  first, 
and  that  from  the  lower  segment  of  the  uterus  follows.  Thus  the  amnion 
and  the  amniotic  surface  of  the  placenta  are  on  the  outside  of  the  after- 
birth. The  denuded  uterine  mucosa  is  gradually  restored  to  its  normal 
condition.  As  after  menstruation,  the  epithelium  spreads  from  the  glands 
over  the  tunica  propria. 

The  entire  after-birth,  since  its  delivery  follows  that  of  the  child,  was  called  the 
secunda  or  secundina  by  the  ancient  anatomists.  The  round  flat  mass  which  is  its 
principal  part  was  named  the  placenta  by  Fallopius,  from  its  fancied  resemblance  to 
a  pan-cake.  Long  before  this,  the  membranes  enveloping  the  embryo  were  known  as 
the  chorion,  allantois,  and  amnion,  and  were  described  as  the  outer,  middle  and  inner 


DECIDUAL    MEMBRANES  373 

layers  respectively.  These  ancient  terms  are  of  obscure  derivation.  Chorion  (Gr., 
xtpiov)  is  the  same  as  the  Latin  corium,  which  is  applied  to  the  vascular  layers  of  the 
skin.  In  its  Greek  form  it  is  used  to  designate  the  vascular  chorioid  coat  of  the  eye, 
and  the  chorioid  plexuses  of  the  brain,  but  it  refers  particularly  to  the  vascular  embryonic 
membrane.  Amnion  is  derived  indirectly  from  d//,vos  (a  sheep)  and  Hyrtl  reason- 
ably asks  "How  came  the  sheep  to  have  his  name  enrolled  in  anatomy?"  Whether 
the  amnion  was  first  observed  in  the  sheep,  or  was  so  named  because  of  its  softness, 
or  for  some  very  different  reason,  is  discussed  by  the  early  commentators.  The 
allanlois  was  first  observed  in  the  lower  mammals  in  which  it  attains  great  size.  For 
example,  in  the  sheep  and  pig  it  forms  an  elongated  sac  filled  with  fluid  and  attached 
like  the  arms  of  a  "T"  to  the  distal  end  of  the  allantoic  duct.  This  duct,  which 
corresponds  with  the  entire  human  allantois,  issues  from  the  ventral  abdominal  wall 
and  divides  into  its  two  branches,  as  seen  indistinctly  through  the  chorion  in  Fig. 
372  (over  the  body  of  the  embryo).  The  allantoic  sac  extends  almost  the  entire  length 


FIG.  372. — A  PIG  EMBRYO  REMOVED  FROM  THE  UTERUS,  "SURROUNDED  BY  ITS  THREE  MEMBRANES. 

(Fabricius  ab  Aquapendente,  1687.) 

of  the  chorion,  and  its  ends  break  through  the  chorionic  membrane,  projecting  freely 
as  the  allantoic  appendages.  In  Fig.  372,  the  one  at  the  right  extends  upward,  and 
the  one  at  the  left,  downward.  Such  an  allantois  was  sought  for  in  man,  between  the 
amnion  and  chorion,  where  a  corresponding  structure  should  be  located.  Hale  (1701) 
was  among  those  who  thought  that  he  found  one,  but  he  declared  that  "most  of  the 
ancients  allow  a  human  allantois  not  from  their  experience  of  it,  but  because  they 
took  it  for  granted  that  men  and  other  animals  were  alike  in  their  viscera."  It  was 
not  until  1885  that  it  was  clearly  and  finally  stated  that  the  human  allantois  was 
merely  a  blind  tube  in  the  body  stalk,  never  being  free  or  vesicular  (His,  Anatomic 
menschlicher  Embryonen) . 

As  to  the  appropriateness  of  the  term  allantois  (sausage-like,  from  the  Gr.  dAAas 
there  is  difference  of  opinion.  Fabricius  (De  formato  fcetu,  1600)  one  of  whose 
drawings  is  reproduced  in  Fig.  372,  considers  that  the  word  really  means  "intestinal," 
or  like^a  sausage  skin. 

DECIDUA  VERA,  AMNION,  AND  CHORION  L^VE. 

.  The  three  structures  named  above  may  readily  be  included  in  a  single 
vertical  section  of  the  wall  of  the  uterus,  in  the  latter  part  of  pregnancy. 
Care  must  be  taken,  however,  not  to  detach  the  amnion.  In  Fig.  373  the 


374 


HISTOLOGY 


amnion  is  seen  on  the  upper  surface  of  the  section,  having  its  simple  cu- 
boidal  or  flat  epithelium  toward  the  embryo,  and  its  mesodermic  connec- 


Amnion. 


Chorion 


Compact  layer. 


Cavernous  layer.    J*«f^" 


-  Vein. 


$-  — Gland. 


Vi&— Vem- 


Muscularis. 


FIG.  373. — VERTICAL  SECTION  THROUGH  THE  WALL  OF  A  UTERUS  ABOUT  SEVEN    MONTHS  PREGNANT 
WITH  THE  MEMBRANES  IN  SITU.     X  30.     (Schaper.) 

tive  tissue  toward  the  chorion.     Adhesions  in  the  form  of  slender  strands 
bind  it  to  the  connective  tissue  of  the  chorion.     The  chorionic  epithelium 

forms  a  layer  over  the  surface  of  the  vera;  it 
presents  slight  irregularities  but  is  without 
villi.  The  superficial  uterine  epithelium  has 
degenerated;  it  disappeared  in  an  earlier 
stage.  The  modified  mucosa,  or  decidua 
vera,  is  divisible  into  a  superficial  compact 
layer  and  a  deep  cavernous  layer.  After  the 
epithelium  of  the  glands  in  the  compact 
layer  had  degenerated  and  was  resorbed,  the 
connective  tissue  came  together  obliterating 
the  gland  cavities.  The  compact  layer  is 
therefore  without  glands.  The  cells  of  the 
tunica  propria  have  enlarged,  and  become 
decidual  cells  (Fig.  374).  These  cells,  which 
occur  only  in  pregnancy,  are  flattened,  round, 
oval  or  branched  structures  of  large  size  (0.03 
to  o.i  mm.).  Usually  they  contain  a  single  nucleus  but  often  there  are 
two  or  more,  and  in  giant  forms  there  may  be  thirty  or  forty.  The 


FROM 
OF     A 


FIG.  374. — DECIDUAL  CELLS 
THE  Mucous  MEMBRANE 
HUMAN  UTERUS  ABOUT  SEVEN 
MONTHS  PREGNANT.  One  cell 
shows  a  mitotic  figure.  X  250. 
(Schaper.) 


DECIDUAL    MEMBRANES 


375 


cavernous  layer  of  the  mucosa  contains  slender  clefts  parallel  with  the 
muscularis.  These  are  glands  which  have  been  stretched  laterally;  some 
of  them  retain  areas  of  normal  epithelium,  but  in  many  the  epithelium  has 
degenerated,  and  from  some  it  has  wholly  disappeared.  The  connective 
tissue  is  but  slightly  modified.  Throughout  the  decidua,  but  especially 
in  the  superficial  portion,  the  vessels  are  greatly  distended. 


PLACENTA. 

The  chorionic  villi,  the  interlacing  branches  of  which  form  the  fetal 
portion  of  the  placenta,  are  shaped  as  in  Fig.- 3 7 5.  The  finding  of  such 
structures  in  a  uterine  discharge  or  curetting  is  diagnostic  of  preg- 
nancy. The  villi  in  the  earliest  stages  are  composed  entirely  of  epi- 
thelium, but  they  soon  acquire  a  core  of  the  chorionic  mesenchymal  tissue, 
in  which  are  the  terminal  branches  of  the  umbilical  vessels.  The  epi- 
thelium is  very  early  divisible  into  two  layers.  The  outer  layer  consists 


XI9 


XI9 


FIG.  375. — ISOLATED  TERMINAL  BRANCHES  OF  CHORIONIC  VILLI;  THAT  ON  THE  LEFT  is  FROM  AN  EMBRYO 
OF  TWELVE  WEEKS;  ON  THE  RIGHT,  AT  FULL  TERM.     (Minot.) 

of  densely  staining  protoplasm,  said  to  contain  fat  granules  and  to  pre- 
sent a  brush  border;  it  has  dark,  round  or  flattened  nuclei.  Since  cell 
boundaries  are  lacking,  this  is  called  the  syncytial  layer  (Fig.  376). 
Mitotic  figures  are  seldom  seen  in  it.  Generally  its  nuclei  are  in  a  single 
layer  at  varying  distances  from  one  another,  but  they  may  accumulate 
in  "knots"  or  "proliferation  islands,"  especially  in  late  stages  (Fig.  377). 
The  knots  project  from  the  surface  of  the  villi,  so  that  in  certain  planes 
of  section  they  appear  completely  detached  and  suggest  multinucleate 
giant  cells.  The  syncytial  layer  perhaps  completely  invests  the  villi  at 
first,  but  later  it  is  interrupted  in  many  places. 


376 


HISTOLOGY 


The  deeper  layer  of  the  chorionic  epithelium  consists  of  distinct  cells 
with  round  nuclei  and  clear  protoplasm.  Although  this  is  a  single  layer 
at  the  base  of  young  villi,  it  produces  great  masses  of  cells  at  their  tips. 
These  columns  or  caps  of  cells  in  which  the  villi  terminate  fuse  with  one 


Syncytium. 


Cuboidal  cells  of  the 
basal  layer. 


Connective  tissue. 


Blood  vessel  containing 
nucleated  red  cor- 
puscles. 


Oblique  section  of  the  epithelium. 
FIG.  376. — CROSS  SECTION  OF  A  HUMAN  CHORIONIC  VILLUS  OF  THE*FOURTH^WEEK  OF  PREGNANCY 


Epithelium - 

Epithelial  nucl  eus. 

Capillaries*^-- 


Syncytial  knot. 


Small  artery. 


Syncytial  knot.  __ 


« Syncytial  knot. 


Epithelium. 


Capillary. 


±j 

FIG.   377- — CROSS  SECTION  THROUGH  A  SMALLER  (A)  AND  A  LARGER  (B)  CHORIONIC  VILLUS  OF  A  HUMAN 
PLACENTA  AT  THE  END  OF  PREGNANCY.     X2$o.     (Schaper.) 

another  next  the  decidua,  and  the  uterine  tissue  seems  to  be  dissolved  as 
this  mass  of  epithelium  proliferates.  All  the  superficial  epithelium  of  the 
decidua  basalis  degenerates  and  disappears,  and  the  underlying  parts  of 
the  blood  vessels  in  the  tunica  propria  are  destroyed.  The  uterine  blood 


DECIDUAL    MEMBRANES 


377 


escapes  into  the  intervillous  spaces,  bounded  by  the  syncytium,  or  where 
this  is  deficient,  by  the  basal  cells.  The  maternal  blood  circulates  in  the 
intervillous  spaces  as  shown  in  the  diagram  Fig.  378,  and  does  not  clot. 
So  extraordinary  is  this,  that  attempts  have  been  made  to  detect  an  endo- 
thelial  covering  for  the  villi,  but  without  success.  (The  syncytial  layer 
has  been  considered  endothelial  or  otherwise  of  maternal  origin,  but  this 
view  is  not  accepted.)  It  is  said  that  the  products  of  the  disintegration 
of  the  maternal  tissue,  including  haemoglobin  and  even  entire  red  cor- 
puscles, are  taken  up  by  the  syncytium  and  used  for  the  nutrition  of  the 
embryo. 


Decidua 
basalis. 


Compact 
layer. 


Cavernou 
layer. 


Muscularis. 


Chorionic  villi. '  JT; 

1^1  Intervillous  spaces, 
j  Floating  villus., _ 

j  Attached  villi. 
Vein. 

Spiral  artery. 
j  Gland. 

Vein. 


FIG.  378. — DIAGRAM'OF  THE  HUMAN  PLACENTA  AT  THE  CLOSE  OF  PREGNANCY.     (Schaper.) 


The  placenta  at  birth,  being  an  inch  thick,  presents  in  cross  section  a 
vast  number  of  the  branches  of  villi  cut  in  various  planes.  A  small  frag- 
ment is  shown  in  Fig.  379.  On  the  left,  there  is  a  section  of  a  large  villus, 
containing  fibrous  tissue  of  the  loose  embryonic  type,  in  some  cases  form- 
ing a  thin  basement  membrane  beneath  the  epithelium.  Each  villus 
contains  a  branch  of  the  umbilical  artery  which  ends  in  capillaries  of  very 
large  but  varying  caliber.  They  are  situated  close  beneath  the  epithelial 
layer,  through  which  nutriment  is  transferred  from  the  maternal  blood 
in  the  intervillous  spaces  to  that  of  the  embryo  in  the  vessels  of  the  villi. 
Maternal  and  fetal  blood  never  mingle,  as  may  readily  be  seen  in  early 
stages  when  the  embryonic  blood  contains  nucleated  red  corpuscles. 

The  two  primary  layers  of  the  chorionic  epithelium  are  difficult  to 
recognize  in  many  parts  of  the  placenta  at  birth.  Thus  in  the  villi  shown 
in  Fig.  377  it  is  seen  that  the  epithelium  is  in  places  hardly  distinguishable 
from  the  connective  tissue.  This  thin  portion  may  represent  the  basal 


378 


HISTOLOGY 


layer  and  the  dark  clumps  of  nuclei  scattered  over  its  surface  may  arise 
from  the  syncytium,  but  the  reverse  relation  of  the  two  types  of  epithe- 
lium to  the  original  layers  is  sometimes  stated.  Frequently  the  villi 
are  covered  in  part  with  very  conspicuous  masses  of  hyaline  material, 
apparently  derived  from  epithelial  degeneration  (Fig.  379).  Deposits  of  a 
substance  staining  deeply  with  eosin  and  resembling  the  fibrin  of  blood 
clots  may  also  be  observed.  This  material  is  often  in  the  form  of  layers, 
with  intervals  between  them,  and  is  known  as  "  canalized  fibrin."  It  is 
believed  to  be  derived  from  the  blood,  but  the  origin  of  these  deeply 
staining  masses  is  "not  yet  fully  understood"  (Stohr). 


Connective  tissue. 


Hyaline  substance  in  tan- 
gential section. 


Syncytium. 


Blood  vessel  Hyaline  substance  Proliferation  islands 

FIG.  379. — FROM  A  SECTION  OF  A  HUMAN  PLACENTA  AT  TERM.     X  260. 


The  surface  of  the  placenta  toward  the  embryo  is  covered  with  amnion, 
which  has  remained  in  place  in  the  section  shown  iii  Fig.  380.  Sometimes 
it  becomes  detached  in  preparing  the  specimen.  It  consists  of  homogene- 
ous connective  tissue  toward  the  chorion,  and  is  covered  on  its  free  surface 
by  simple  low  columnar  epithelium,  sometimes  containing  fat  droplets  and 
vacuoles.  The  chorionic  membrane  is  a  much  thicker  layer,  consisting 
of  vascular  connective  tissue,  and  covered  with  epithelium  continuous  with 
that  of  the  villi.  The  root  of  a  villus  is  cut  tangentially  in  Fig.  380.  The 
epithelium  at  term  is  often  in  relation  with  the  hyaline  material  or  "canal- 


DECIDUAL    MEMBRANES 


379 


ized  fibrin"  which  partially  replaces  it.  In  Fig.  380,  cells  of  the  deeper 
layer  of  the  chorionic  epithelium  may  still  be  recognized,  but  these  are 
often  lacking. 

Toward  the  uterine  wall  the  placenta  is  formed  by  the  decidua 
basalis,  which,  like  the  decidua  vera,  includes  a  superficial  compact  layer 
and  a  deeper  cavernous  layer.  The  compact  layer,  which  is  detached 
with  the  placenta  at  birth,  consists  of  connective  tissue,  blood  vessels, 
giant  cells  and  decidual  cells  (Fig.  381).  Some  of  the  chorionic  villi 


Amniotic  epithelium. 
Homogeneous  layer.  — ~ 


;  .  •  *  •    %j 

i;4    •.<    *  * 

h     *    &    w  -^ 


^  "  »B 


Leucocytes.  ^ 


Connective  tissue  of 
the  chorion. 


Chorionic  epithelium,   -fii 


Hyaline  substance. 

Syncytium 
Connective  tissue. . 


x?ar 
—?<*..•  V  '• 


Red  corpuscles. 


4'; . 

_j5^ 

^VJt3fe«fc  '":  _^  J*/"^^  Chorionic  villus. 


Blood  vessels. 
FIG.  380. — FROM  A  SECTION  OF  THE  HUMAN  PLACENTA  AT  TERM.    X    200. 


have  free  endings  toward  this  layer;  others  are  extensively  fused  with 
it,  forming  such  masses  as  shown  on  the  right  of  Fig.  381. 

The  decidua  basalis  extends  out  among  the  villi  in  the  form  of  septa, 
which  subdivide  the  mass  of  villi  into  lobes  or  cotyledons.  (In  the  rumi- 
nants, the  cotyledons  are  widely  separated  by  areas  of  smooth  chorion,  but 
in  man  they  are  closely  adjacent,  with  septa  between  them.)  The  septa 
end  before  reaching  the  chorionic  membrane,  except  at  the  placental 
margin,  where  they  form  an  enclosing  wall.  As  the  uterine  arteries 
approach  the  intervillous  spaces  of  the  chorion,  they  pursue  a  coiled  course, 
so  that  they  may  be  cut  several  times  in  one  section  (Fig.  378).  They  pass, 


38o 


HISTOLOGY 


without  branching,  into  the  septa  of  the  placenta,  and  before  they  empty 
into  the  intervillous  spaces,  their  walls  are  reduced  to  mere  endothelium. 
The  veins  which  drain  the  intervillous  spaces  are  not  found  in  the  septa, 
except  at  the  placental  margin.  They  pursue  an  oblique  course  downward 
from  the  floor  of  the  cotyledons,  beginning  as  large  thin-walled  tubes,  into 
which  free  ends  of  villi  may  project  (Fig.  378). 


— ^»Decidual~cells. 


_^  Connective  tissue. 


Cell  knots. 


FIG.  381. — FROM  A  SECTION  OF  THE  HUMAN  PLACENTA  AT  TERM.     X26o. 


UMBILICAL  CORD. 

The  umbilical  cord  is  a  translucent,  glistening,  white  or  pearly  rope 
of  tissue  about  2  feet  in  length,  extending  from  the  umbilicus  to  the 
placenta.  It  consists  of  mucous  tissue  (p.  62)  covered  with  epithelium, 
and  contains  at  birth  three  large  blood  vessels,  two  umbilical  .arteries  and 
one  umbilical  vein  (Fig.  382,  B).  The  parallel  arteries  generally  wind 
around  the  vein  making  sometimes  forty  revolutions.  The  surface  of  the 
cord  shows  corresponding  spiral  markings  and  often  irregular  protuberances 
called  false  knots.  (True  knots,  tied  by  the  intrauterine  movements  of  the 
embryo,  are  very  rare.)  There  are  no  lymphatic  vessels  or  capillaries  in 
the  cord,  and  the  large  blood  vessels  do  not  anastomose.  The  walls  of  the 
arteries  contain  many  muscle  fibers  but  very  little  elastic  tissue,  and  they 
are  usually  found  collapsed  in  sections;  their  contraction  is  of  interest  since 
nerves  have  been  traced  into  the  cord  for  only  a  very  short  distance.  The 
vein  generally  remains  open. 


UMBILICAL    CORD  381 

The  umbilical  arteries  arise  in  young  embryos  as  the  main  terminal  branches  into 
which  the  dorsal  aorta  bifurcates.  These  vessels  curve  ventrally  on  either  side  of 
the  pelvis  and  pass  out  through  the  cord  to  the  chorion;  they  are  equidistant  from  the 
allantois  which  they  accompany.  In  the  adult  the  parts  of  these  vessels  near  the 
aorta  are  known  as  the  common  iliac  arteries,  and  the  small  offshoots  from  them  which 


FIG.  382. — CROSS  SECTION  OF  UMBILICAL  CORDS. 

A,  from  an  embryo  of  two  months,  X  20;  B,  at  birth,  X  3-    al.,  Allantois;  art.,  artery;  coe.,  coelom;  v.» 

vein;  y.  s.,  yolk  stalk. 

have  grown  down  the  limbs,  have  become  the  external  iliac  arteries.  The  distal  course 
of  the  original  vessels  may  still  be  followed  through  the  hypogastric  arteries  (internal 
iliacs)  up  on  either  side  of  the  median  line  to  the  navel;  toward  the  navel  the  vessels 
have  become  reduced  to  slender  cords.  The  umbilical  vein,  within  the  cord,  represents 
the  fusionVof  a  pair.  On  entering  the  body  it  conveys  the  blood  from  the  placenta, 
through  the  persistent  left  umbilical  vein,  di- 
rectly to  the  under  side  of  the  liver,  which  it 

crosses  as  the  ductus  venosus,  and  then  empties  \>        «  7\Q£^  LOTTIES 

into  the  vena  cava  inferior.  In  the  adult,  its 
former  course  is  marked  by  the  round  ligament  of 
the  liver  and  the  ligament  of  the  ductus  venosus. 


The  allantois,  which  the  umbilical  ves- 
sels accompany,  at  first  extends  the  entire 
length  of  the  cord  as  a  slender  epithelial 
tube.  Its  condition  at  three  months  is 
shown  in  Fig.  383.  At  birth,  it  has  be- 
come reduced  to  a  very  slender,  and  gen- 
erally interrupted,  solid  strand  of  epithe- 
lial cells.  That  it  may  retain  its  con- 
tinuity is  stated  by  Ahlfeld  (Arch.  f. 
Gynak.,  1876,  vol.  10,  p.  81).  This  remnant  may  be  sought  for  near  the 
body  of  the  embryo,  and  its  tendency  to  retain  its  original  position  equi- 
distant from  the  umbilical  arteries  is  the  best  guide  for  locating  it.  By 
the  use  of  Mallory's  connective  tissue  stain,  the  epithelial  cells  may  be 


FIG.  383. — CROSS  SECTION  OF  THE  AL- 
LANTOIC  DUCT,  FROM  THE  UMBILICAL 
CORD  OF  A  HUMAN  EMBRYO  OF  THREE 
MONTHS.  X34O.  (Minot.) 

Ent.,  Entodermal  epithelium;  mes.,  mes- 
enchyma. 


382  HISTOLOGY 

stained  red  in  contrast  with  surrounding  blue  fibrils.  Within  the  body  of 
the  embryo  the  allantois  is  prolonged  to  the  upper  end  of  the  bladder, 
with  which  it  is  continuous;  this  intra-abdominal  part  has  long  been 
called  the  urachus  (i.e.,  vas  urinarium).  If  it  remains  pervious  at  birth, 
which  is  abnormal,  urine  may  escape  at  the  umbilicus. 

The  yolk  stalk,  surrounded  by  an  extension  of  the  body  cavity,  is 
found  in  young  umbilical  cords  (Fig.  382,  A).  This  stalk  is  a  slender  strand 
of  mesoderm,  containing  the  entodermal  vitelline  duct,  and  the  vitelline 
vessels  which  accompany  it  to  the  yolk-sac.  The  loop  of  intestine 
from  which  the  yolk  stalk  springs  may  also  extend  into  the  cavity  of  the 
cord,  and  if  it  has  not  been  drawn  into  the  abdomen  at  birth,  umbilical 
hernia  results.  If  the  cavity  of  the  vitelline  duct  remains  pervious  at 
birth,  the  intestinal  contents  may  escape  at  the  umbilicus.  (Such  a  con- 
dition is  known  as  a  fecal  fistula,  whereas  the  pervious  urachus  constitutes 
a  urinary  fistula.)  Ordinarily  the  yolk  stalk  and  its  vitelline  vessels,  to- 
gether with  the  ccelom  of  the  cord,  have  been  obliterated  before  birth,  so 
that  no  trace  of  them  remains  in  sections  of  the  cord. 


FIG.  384. — YOLK-SAC  AND  PERSISTENT 
VITELLINE  VESSELS,  EXPOSED  BY  RE- 
FLECTING THE  AMNION  AT  THE  DISTAL 
END  OF  THE  CORD.  (Lonnberg.) 


FG.  385.— PART  OF  A  HUMAN  AMNIOTIC 

VlLLUS.       X   330. 

Ep.,  Epitrichium;  S.  C.,  stratum  corneum; 
S.  g.,  stratum  granulosum;  S.  G., 
stratum  germinativum ;  M.  B.,  homo- 
geneous jayer;  F.  T.,  fibrous  tissue; 
A.  T.,  areolar  tissue. 


The  yolk-sac  may  be  found  with  almost  every  placenta,  as  a  very  small 
cyst  adherent  to  the  amnion  in  the  placental  area.  If  the  distal  end  of 
the  cord  is  gently  stretched,  a  wing-like  fold  appears  (Fig.  384),  differing 
from  all  others  by  containing  no  large  vessels;  the  fold  indicates  the  direc- 
tion of  the  yolk-sac,  which  may  be  exposed  by  stripping  the  amnion  from 
the  chorion.  It  may  be  beyond  the  limits  of  the  placenta.  Further 
details  will  be  found  in  Lonnberg's  admirable  Studien  iiber  das  Nabel- 
blaschen,  Stockholm,  1901. 

Amniotic  mill  are  irregular,  flat,  opaque  spots  on  the  amnion  near  the 
distal  end  of  the  cord  They  are  often  present  and  may  suggest  a  diseased 


UMBILICAL    CORD  383 

condition.  As  seen  in  Fig.  385  they  are  areas  of  imperfectly  developed 
skin,  and  as  shown  in  this  case  (Lewis,  Art.  " Umbilical  Cord/'  Buck's 
Hdb.,  2nd  ed.)  they  present  all  of  its  fundamental  layers.  Frequently 
these  cornified  areas  are  less  fully  developed.  They  have  been  compared 
with  the  pointed  epithelial  elevations  which  cover  the  surface  of  the 
umbilical  cord  in  ruminants,  but  the  latter  do  not  appear  as  areas  of 
imperfect  skin,  and  probably  are  entirely  different  structures.  They  may 
appropriately  be  called  villi,  but  the  human  "villi"  scarcely  rise  above 
the  surface.  Their  significance  is  unknown. 


VAGINA  AND  EXTERNAL  GENITAL  ORGANS. 

The  vagina  consists  of  a  mucosa,  submucosa,  muscularis  and  fibrosa. 
Its  epithelium  is  thick  and  stratified,  its  outer  cells  being  squamous  and 
easily  detached.  It  rests  upon  the  papillae  of  the  tunica  propria,  and 
is  thrown  into  coarse  folds  or  ruga.  Glands  are  absent.  The  tunica 
propria  is  a  delicate  connective  tissue  with  few  elastic  fibers,  containing 
a  variable  number  of  lymphocytes.  Occasionally  there  are  solitary 
nodules,  above  which  numerous  lymphocytes  wander  into  the  epithelium. 
The  submucosa  consists  of  loose  connective  tissue  with  coarse  elastic 
fibers.  The  muscularis  includes  an  inner  circular  and  a  small  outer 
longitudinal  layer  of  smooth  muscle.  The  fibrosa  is  a  firm  connective 
tissue,  well  supplied  with  elastic  elements.  Blood  and  lymphatic  vessels 
are  found  in  the  connective  tissue  layers,  and  wide  veins  form  a  close 
network  between  the  muscle  bundles.  There  is  a  ganglionated  plexus  of 
nerves  in  the  fibrosa. 

The  mucous  membrane  of  the  vestibule  differs  from  that  of  the  vagina 
in  possessing  glands.  The  numerous  lesser  vestibular  glands,  0.5-3  mm-  'in 
diameter,  produce  mucus;  they  occur  chiefly  near  the  clitoris  and  the 
outlet  of  the  urethra.  The  pair  of  large  vestibular  glands  (Bartholin's) 
also  produce  mucus;  they  correspond  with  the  bulbo-urethral  glands  in 
the  male  and  are  of  similar  structure.  The  hymen  consists  of  fine-fibered, 
vascular  connective  tissue  covered  with  mucous  membrane.  The  clitoris 
is  an  erectile  body,  resembling  the  penis.  It  includes  two  small  corpora 
cavernosa.  The  glans  clitoridis  contains  a  thick  net  of  veins.  It  is  not, 
as  in  the  male,  at  the  tip  of  a  corpus  cavernosum  urethrae  which  begins 
as  a  median  bulb  in  the  perineal  region;  the  bulbus  in  the  female  exists 
as  a  pair  of  highly  vascular  bodies,  one  on  either  side  of  the  vestibule. 
Each  is  called  a  bulbus  vestibuli.  The  labia  minora  contain  sebaceous 
glands,  0.2-2.0  mm.  in  size,  which  are  not  connected  with  hair  follicles; 
they  first  become  distinct  between  the  third  and  sixth  years.  The  labia 
majora  have  the  structure  of  skin. 


HISTOLOGY 


SKIN. 

The  skin  (cutis)  consists  of  an  ectodermal  epithelium,  the  epidermis, 
and  a  mesodermal  connective  tissue,  the  corium  (Fig.  386).  The  ecto- 
derm is  at  first  a  single  layer  but  it  soon  becomes  double,  the  outer  cells 
staining  more  deeply,  and  being  notably  larger  than  the  inner  cells.  Their 

characteristic  dome  shape  is 
seen  in  the  figure.  The  outer 
layer  has  been  named  the 
epitrichium,  since  the  hairs 
which  grow  up  through  the 
underlying  epithelium  do  not 
penetrate  it,  but  cause  it  to  be  cast  off.  The  epitrichium  has  been 
found  on  the  umbilical  cord  and  in  places  on  the  amnion.  It  may 
possibly  be  related  to  the  chorionic  syncytium.  The  deeper  layer  of 
ectoderm  becomes  stratified,  and  gives  rise  to  the  hairs,  nails,  and 


•  i  ectoderm 
epidermis 

mesoderm 

~  v-7 : :£c^ ;  - ~*>- -^-^  — ;:;:^.::  -  >-«  |     corinm 

FIG.  386. — SKIN  FROM  THE  OCCIPUT  OF  AN  EMBRYO  OF  Two 

AND  ONE-HALF  MONTHS.     (After  Bowen.) 
The  outer  layer  of  dark  cells  is  the  epitrichium. 


Duct  of  a  sweat 
gland. 


Coil  of  a  sweat 
gland. 


Stratum  corneum. 
Stratum  lucidum 

Stratum  granulosum. 
Stratum  germinativum 


Stratum 
papillare. 


Corium. 


Stratum 
reticulare.   , 


Epidermis. 


Stratum  subcutaneum. 


FIG.  387. — VERTICAL  SECTION  FROM  THE  SOLE  OF  THE  FOOT  OF  AN  ADULT.     X  25. 


enamel  organs.  It  also  produces  two  types  of  glands,  the  sebaceous 
glands  which  are  usually  connected  with  hairs,  and  the  sweat  glands. 
These  are  widely  distributed;  locally  the  ectoderm  forms  the  mam- 
mary glands,  ceruminous  glands  of  the  ear,  ciliary  glands  of  the  eyelids, 


SKIN 


385 


and  other  special  forms.  The  greater  part  of  the  surface  of  the  skin 
presents  many  little  furrows,  the  sulci  cutis,  which  intersect  so  that  they 
bound  rectangular  spaces.  On  the  palms  and  soles  the  furrows  are  parallel 
for  considerable  distances,  being  separated  from  one  another  by  slender 
ridges,  the  cristcB  cutis,  along  the  summits  of  which  the  sweat  glands  open. 
The  ridges  are  most  highly  developed  over  the  pads  of  tissue  at  the  finger 
tips,  where  they  present  the  familiar  spiral  and  concentric  patterns. 
These  pads  of  connective  tissue,  the  toruli  tactiles,  must  not  be  confounded 
with  elevations  due  to  underlying  muscles. 


B  c 

- 


Epidermis. 


In  the  pentadactylous  mammals,  each  extremity  typically  presents  five  digital 
toruli,  at  the  tips  of  the  fingers  or  toes;  four  interdigital  toruli,  near  the  metacarpo-  or 
metatarso-phalangeal  joints;  and  two  or  three  proximal  cushions — a  tibial  and  an 
elongated  fibular;  or  a  radial  and  two  ulnar,  one  behind  the  other.  Often  the  inter- 
digital  cushions  fuse,  as  in  the  paw  of  the  cat  and  the  ball  of  the  human  foot,  and  the 
one  between  the  thumb  and  fingers  may  be  suppressed.  These  toruli  are  very  promi- 
nent in  the  embryo.  According  to 
Miss  Whipple  (Zeitschr.  f.  Morph.  u. 
Anthr.,  1904,  vol.  7,  pp.  261-368) 
they  are  primarily  walking  pads, 
with  ridges  at  right  angles  to  the  slip- 
ping force.  Usually  they  are  con- 
sidered primarily  tactile.  The  ex- 
tensive literature  pertaining  to  them 
has  been  reviewed  by  Schlagenhaufen 
(Anat.  Hefte,  1906,  Abt.  II,  vol.  15, 
pp.  628-662). 

,  Corium. 

Corium.  The  corium  is  a 
layer  of  densely  interwoven 
bundles  of  connective  tissue  ex- 
tending from  the  epidermis  to 
the  fatty,  areolar  subcutaneous 
tissue  (Fig.  387).  Toward  the 
epidermis  the  corium  forms  pa- 
pilla, which  vary  considerably  in  size  and  number  in  different  parts  of  the 
body.  They  are  tallest  (even  0.2  mm.  high)  and  most  numerous,  often 
being  branched,  in  the  palms  and  soles.  Beneath  the  epidermal  ridges 
they  may  occur  quite  regularly  in  double  rows  (Fig.  388),  as  long  since 
'observed  by  Malpighi.  In  the  skin  of  the  face  the  papillae  are  poorly 
developed,  and  in  advanced  age  they  may  wholly  disappear.  The  papillae 
are  composed  of  cellular  connective  tissue,  which  forms  a  tunica  propria; 
and  each  papilla  contains  a  terminal  knot  of  capillary  blood  vessels,  or  a 
tactile  corpuscle  (Fig.  152,  p.  159).  The  corpuscles  are  most  numerous 
in  the  sensitive  finger  tips,  where  they  may  be  found  in  one  papilla  in 
every  four. 


Papillae  under 
the  ridge  A. 


FIG. 


Tactile 
corpuscle. 

. — VERTICAL  SECTION  FROM  THE  SOLE  OF  THE 


Papillae  under 
the  ridge  D. 


FOOT  OF  AN  ADULT,  SHOWING  FOUR  RIDGES  (A-D) 
WITH  A  PAIR  OF  PAPILL^B  BENEATH  EACH.  Between 
the  papillae  of  D  is  the  duct  of  a  sweat  gland.  X  25. 


386 


HISTOLOGY 


The  entire  corium  is  somewhat  arbitrarily  subdivided  into  an  outer 
stratum  papillare  and  an  inner  stratum  reticulare  (Fig.  387).  These  layers 
blend  with  one  another,  but  the  outer  portion  consist  of  finer  bundles  of 
connective  tissue,  more  closely  interwoven  than  those  in  the  coarse  net- 
work characteristic  of  the  stratum  reticulare.  Beneath  the  skin,  but  in- 
separable from  it,  is  the  stratum  subcutaneum,  which  is  composed  of  areolar 
tissue  with  large  areas  of  fat  cells;  where  the  fat  forms  a  continuous  layer, 
it  is  known  as  the  panniculus  adiposus.  ,  Finally  the  bundles  of  the  stratum 
subcutaneum  connect  more  or  less  intimately  with  the  fascia  around  the 
muscles,  or,  in  places,  with  the  periosteum. 

The  elastic  fibers  of  the  corium  form  evenly  distributed  networks, 
which  are  finer  in  the  stratum  papillare  and  coarser  in  the  stratum 
reticulare.  There  is  said  to  be  a  subepithelial  network,  and  a  layer  of 

Depressions  which 
were  occupied  by 
papillae. 


Ridge  corresponding 

to  a  furrow  of  the 

corium. 


Portion  of  the  duct  of 
a  sweat  gland. 


FIG.  389. — EPIDERMIS  DETACHED  FROM  THE  DORSUM  OF  THE  HUMAN  FOOT,  SEEN 

FROM  THE  LOWER  SURFACE.     X  120. 
The  dark  epithelial  network  between  the  papillae  is  the  rete  Malpighii. 

numerous  coarse  fibers  immediately  above  the  general  layer  of  fascia. 
In  old  age  a  notable  decrease  in  the  elastic  fibers  has  been  recorded. 
The  muscle  fibers  of  the  corium  are  chiefly  the  small  bundles  of  smooth 
muscle  attached  to  the  sheaths  of  the  hairs,  forming  the  arrectores 
pilorum.  Smooth  muscle  is  diffusely  distributed  in  the  nipple,  and  in  the 
scrotum  it  forms  a  layer  pervaded  by  elastic  tissue,  known  as  the  tunica 
dartos.  Striated  muscle  fibers  derived  from  the  muscles  of  expression 
terminate  in  the  skin  of  the  face.  The  vessels  and  nerves  of  the  corium 
are  described  on  page  399. 

Epidermis.  If  a  piece  of  skin  is  boiled,  the  epidermis  may  be  stripped 
off,  carrying  the  tunica  propria  with  it;  and  the  epidermis  itself  may  be 
separated  into  two  layers.  The  outer  'layer  is  the  stratum  corneum;  the 
inner  is  the  stratum  germinativum. 

The  stratum  germinativum  was  formerly  called  the  stratum  mucosum  or  rete 
Malpighii.  It  was  first  described  by  Malpighi  who  recognized  its  soft  or  "mucous" 


SKIN 


387 


nature,  and  referred  to  it  as  a  rete  since  it  forms  a  network  between  the  papillae  of 
the  corium  (Fig.  389).  Malpighi  considered  that  the  color  of  the  Ethiopian  skin  was 
confined  to  this  layer. 

The  stratum  germinativum  and  stratum  corneum  are  subdivisions  of  a 
single  thick  stratified  epithelium.  The  .basal  cells,  which  rest  directly 
upon  the  papillae  of  the  corium,  constitute  a  single  row  of  columnar  cells, 
with  elongated  nuclei  and  no  cell  walls  (Fig.  390).  Through  mitotic 
division  these  cells  multiply  and  give  rise  to  the  outer  polygonal  cells, 
but  it  is  noteworthy  that  mitotic  figures  are  seldom  seen.  The  polygonal 
cells  which  form  the  bulk  of  the  stratum  germinativum  are  connected  with 
one  another  by  slender  intercellular  bridges  (Fig.  43,  p.  53),  through  which 
fibrils  pass  from  cell  to  cell.  Because  of  this  striking  feature,  the  stratum 
germinativum  was  formerly  called  the  stratum  spinosum. 


M't'---- 

w*  * 


^- 


Stratum 
germinativum. 


Corium 
^(Tunica 
propria.) 


>'  2 


FIG.  390. — THE  DEEPER  PART  OF  THE  EPIDERMIS,  FROM  THE  SOLE 
OF  THE  FOOT  OF  AN  ADULT  MAN.      X  360. 

The  transition  from  the  stratum  germinativum  to  the  stratum  corneum 
is  abrupt.  It  may  be  marked  by  an  incomplete  layer  of  coarsely  granular 
cells,  such  as  are  highly  developed  in  the  skin  of  the  palms  and  soles,  where 
they  form  the  stratum  granule  sum  (Fig.  390).  In  the  stratum  corneum 
the  cells  acquire  a  horny  exoplasmic  membrane;  the  bridges  become 
short  stiff  spines;  the  protoplasm  and  nucleus  are  dry  and  shrunken;  and 
in  the  outermost  cells  the  nucleus  wholly  disappears.  The  cells  become 
flatter  toward  the  surface,  from  which  they  are  constantly  being  des- 
quamated. 


388 


HISTOLOGY 


The  process  of  cornification  presents  a  more  elaborate  picture  in 
sections  of  the  palms  and  soles.  Outward  from  the  stratum  germinativum 
there  is  a  darkly  staining,  coarsely  granular  layer,  one  or  two  cells  thick, 
which  is  followed  by  a  clear,  somewhat  refractive  band  in  which  the  cell 
outlines  are  indistinct.  This  layer  seems  saturated  with  a  dense  fluid 
formed  by  dissolution  of  the  underlying  granules.  In  haematoxylin 
and  eosin  specimens,  the  granular  layer  or  stratum  granulosum  is  followed 
by  a  pink  and  then  by  a  bluish  band,  which  are  subdivisions  of  the  clear 
stratum  lucidum.  These  are  followed  by  a  very  thick  stratum  corneum. 
Except  in  the  palms  and  soles,  the  granulosum  is  thin  and  the  lucidum  is 
absent.  Chemically. the  coarse  granules  of  the  stratum  granulosum  resem- 
ble the  horny  substance  keratin  (from  which  they  differ  by  dissolving  in 
caustic  potash);  they  are  therefore  called  kerato-hyalin  granules.  Their 
diffuse  product  in  the  stratum  lucidum  is  named  eleidin.  In  the  corneum 
it  becomes  par  eleidin,  which,  like  fat,  blackens  with  osmic  acid,  but  the 
reaction  occurs  more  slowly.  The  pareleidin  is  not  due  to  fat  entering 
the  skin  from  oily  secretions  on  its  outer  surface.  Further  information 
regarding  these  substances  is  supplied  by  Pinkus  (Keibel  and  Mall's 
Human  Emtryology,  vol.  i). 

The  color  of  the  skin  is  due  to  fine  pigment  granules  in  and  between 
the  lowest  layers  of  the  epidermal  cells.  Underlying  cells  of  the  corium 
sometimes  contain  groups  of  finer  pigment  granules,  but  such  cells  are 
absent  from  the  palms  and  soles  and  are  infrequent  elsewhere.  They 
may  be  found  in  the  deeply  pigmented  circum-anal  tissue,  and  in  the 
eyelids. 

\  • 

NAILS. 

The  nails  are  areas  of  modified  skin  consisting  of  corium  and  epi- 
thelium. The  corium  is  composed  of  fibrous  and  elastic  tissue,  the  bundles 


Stratum 
germinativum. 


Eponychium. 


Nail  wall. 


Nail  groove. 

Bone  of  third 
phalanx. 

PIG.  391. — DORSAL  HALF  OF  A  CROSS  SECTION  OF  THE  THIRD  PHALANX  OF  A  CHILD.     X  15. 
The  ridges  of  the  nail  bed  in  cross  section  appear  like  papillae. 

of  which  in  part  extend  vertically  between  the  periosteum  of  the  phalanx 
and  the  epithelium,  and  in  part  run  lengthwise  of  the  finger.  In  place  of 
papillae,  the  corium  of  the  nail  forms  narrow  longitudinal  ridges,  which 


NAILS 


339 


are  low  near  the  root  of  the  nail  but  increase  in  height  toward  its  free 
distal  border;  there  they  abruptly  give  place  to  the  papillae  of  the  skin. 
The  epithelium  consists  of  a  stratum  germinativum  and  a  stratum  corneum. 
The  latter,  according  to  Bowen  (Anat.  Anz.,  1889,  vol.  4,  pp.  421-450), 
represents  a  greatly  thickened  stratum  lucidum,  but  this  opinion  requires 
confirmation.  In  the  embryo  the  horny  substance  is  entirely  covered  by 
a  looser  layer,  the  eponychium,  and  this  name  is  applied  in  the  adult  to 
the  skin-like  tissue  which  overlaps  the  root  and  sides  of  the  nail  (Fig.  391). 
The  eponychium  is  the  stratum  corneum  of  the  adjoining  skin. 

It  is  now  generally  considered  that  the  cells  of  the  stratum  germinati- 
vum covering  the  greater  part  of  the  "nail  bed"  do  not  produce  any  of  the 
overlying  horny  material.  This  function  is  reserved  for  the  germinative 
cells  at  the  root  of  the  nail,  beneath  the  crescentic  white  area,  the  lunula, 
and  its  extension  backward  under  the  nail  fold.  The 
latter  is  a  fold  of  skin  which  is  deep  at  the  root  of  the 
nail,  but  becomes  shallower  as  it  extends  forward  on 
either  side,  bounded  by  the  nail  wall  (Fig.  391).  It  is 
now  stated  that  cornification  in  the  nails  takes  place  with- 
out the  formation  of  kerato-hyalin  granules,  and  a  fibrillar 
arrangement  of  the  keratin  has  been  thought  to  account 
for  the  whiteness  and  opacity  of  the  lunula.  The  corni- 
fied  cells  of  the  nail  may  be  separated  by  placing  a  frag- 
ment in  a  strong  solution  of  caustic  potash  and  heating  to  boiling.  The 
cells  differ  from  those  in  the  outer  layers  of  the  skin  by  retaining  their 
nuclei  (Fig.  392). 


FIG.  392  —  CELLS 
OF  A  HUMAN 
NAIL.  X  240. 


Epidermis. 


Epithelial  column. 


HAIR. 

Development.     The  hairs  arise  as  local  thickenings  of  the  epidermis. 

They  soon  become  round  columns  of 
ectodermal  cells  extending  obliquely 
downward  into  the  corium  (Fig.  393). 
As  the  columns  elongate  the  terminal 
portion  becomes  enlarged,  forming  the 
bulb  of  the  hair,  and  a  mesodermal 
papilla  occupies  the  center  of  the  bulb. 
On  that  side  of  the  epithelial  column 
which  from  its  obliquity  may  be  called 
the  lower  surface,  there  are  found  two 

Mesenchyma.  ,,.  /_,.  ^\          „.. 

FIG.  393-VEHTicAL  SECTION  OP  THE  SKIN  OK  swelhngs  (Figs.  394-396) .     The  upper 
MoN?HsKxF2A3SUMANEMBRYOOFFlVE  is  to  become  a  sebaceous  gland,    dis- 
charging its  secretion  into  the  epithelial 
column;  the  lower  or  deeper  swelling  is  called  the  " epithelial  bed,"  and 


Mesenchyma 


39° 


Epidermis. 


Epithelial       Part  of  a 
hair 
column. 


•Papilla. 


FIG.  394.- — VERTICAL  SECTION  OF  THE 
SKIN  OF  THE  GLUT.EAL  REGION 
OF  A  HUMAN  EMBRYO  OF  FIVE 
MONTHS.  X  230. 


FIG.  395  .—VERTICAL  SECTION  OF  THE 
SKIN  OF  THE  BACK  OF  A  HUMAN 
EMBRYO  OF  FIVE  AND  A  HALF 
MONTHS.  X  230. 


Tangential  section  of  the  outer  sheath. 


Cornified  inner  sheath. 


Cell  nuclei  of  the 

Inner   f  Huxley's 

sheath.l  „    *n,d  ?f 

(.  Henle  s  layer. 


FIG.  396. — VERTICAL  SECTION  OF  THE  SKIN  OF  THE  FOREHEAD  OF  A  HUMAN 
EMBRYO  OF  FIVE  MONTHS.     X23O.     Differentiation  of  the  sheaths  of  the  hair. 


HAIR 


391 


Blood  vessel. 


Hair  canal. 


its  cells,  which  increase  by  mitosis,  contribute  to  the  growth  of  the  col- 
umn. (The  lower  swelling  is  often  described  as  the  place  of  insertion 
of  the  arrector  pili  muscle).  Beginning  near  the  bulb,  the  core  of  the 
column  separates  from  the  peripheral  cells;  the  latter  become  the  outer 
sheath  of  the  hair.  The  core  forms  the  inner  sheath  and  the  shaft  of  the 
hair.  The  cells  of  the  shaft  become  cornified  just  above  the  bulb,  and 
they  are  surrounded  by  the  inner  sheath  as  far  as  the  sebaceous  gland. 
Beyond  this  point  the  inner  sheath  degenerates,  so  that  in  later  stages 
the  distal  part  of  the  shaft  is  immediately  surrounded  by  the  outer 
sheath.  As  new  cells  are 
added  to  the  hair  from 
below,  the  shaft  is  pushed 
toward  the  surface.  The 
central  cells  in  the  outer 
end  of  the  column  degen- 
erate, thus  producing  a 
"hair  canal"  which  is  pro- 
longed laterally  in  the  epi- 
dermis (Fig.  397).  The 
shaft  enters  the  canal, 
breaks  up  the  overlying 
epitrichium,  and  projects 
from  the  surface  of  the 
body.  That  portion  of  the 
hair  which  remains  be- 
neath the  epidermis  is 
called  its  root.  In  addi- 
tion to  the  epithelial 
sheaths,  the  root  in  all 

larger  hairs  possesses  a  connective  tissue  sheath,  derived  from  the  corium. 
This  serves  for  the  insertion  of  a  bundle  of  smooth  muscle  fibers,  the  other 
end  of  which  is  connected  with  the  elastic  and  fibrous  elements  in  the  super- 
ficial part  of  the  corium.  Since  this  muscle  by  contraction  causes  the 
hair  to  stand  on  end,  it  is  called  the  arrector  pili.  Its  insertion  is  always 
below  the  sebaceous  gland  and  on  the  lower  surface  of  the  hair,  as  shown 
in  Fig.  398.  The  hairs  which  cover  the  body  of  the  embryo,  persisting 
after  birth  to  a  variable  extent,  are  soft  and  downy,  and  are  known 
as  lanugo.  Arrector  muscles  are  absent  from  the  lanugo  of  the  nose, 
cheeks  and  lips,  and  also  from  the  eyelashes  (cilia)  and  nasal  hairs 
(vibrissae). 

Adult  Structure.  The  general  appearance  of  hairs  in  sections  of  the 
adult  skin  is  shown  in  Fig.  398,  which  includes  also  the  sebaceous  glands 
emptying  into  the  sheaths  of  the  hairs,  and  sweat  glands  which  are  usually 


.  - •'- —  -.-"  ••  -     Degenerating  inner 


Epithelial  bed. 


Outer  sheath. 


FIG.  397. — VERTICAL  SECTION  OF  THfc  SKIN  OF  THE  BACK  OF  A 

HUMAN  EMBRYO  OF  FIVE  AND  A  HALF  MONTHS.     X  120. 

The  staining  with  iron  haematoxylin  has  made  the  horny  parts  so 

black  that  their  details  are  invisible. 


392 


HISTOLOGY 


entirely  separate  structures.  Occasionally  a  sweat  gland  opens  into  the 
sheath  of  a  hair  near  its  outlet.  Each  hair  consists  of  a  papilla,  bulb  and 
shaft,  together  with  sheaths  around  the  root,  namely  an  inner  and  outer 
epithelial  sheath  and,  external  to  these,  a  connective  tissue  sheath. 
These  structures,  together  with  the  arrector  pili  muscle  which  is  inserted 
into  the  connective  tissue  sheath,  are  indicated  in  Fig.  398,  but  they  are 

Shaft  of  a  hair. 
Stratum  corneum.  — j 

Stratum  germinativum.  — #r- 


Inner  epithelial  sheath.—- f^-r^j 
Medulla.— -A"-' 


Corcex -f.-  "-.- 

Conn,  tissue  sheath. -^jjL:l 

Bulb J 

Papilla.  --|| 

Stratum  aubcutaneum.  • S-r£ 

Epicranial  tendon —77- 


FIG.  398. — THICK  SECTION  OF  THE  HUMAN  SCALP.     X  20. 

shown  in  detail  in  the  longitudinal  section,  Fig.  399,  and  in  the  transverse 
sections,  Figs.  401-405.     They  may  be  described  as  follows: 

The  connective  tissue  sheath,  derived  from  the  corium,  is  found  around 
the  roots  of  the  coarser  hairs,  but  is  absent  from  the  lanugo.  It  may  be 
subdivided  into  three  concentric  layers.  The  outermost  consists  of  loose 
'connective  tissue  with  longitudinal  fibers,  and  contains  elastic  tissue  and 
numerous  vessels  and  nerves.  The  middle  layer,  which  is  thicker,  consists 
of  circular  bundles  of  connective  tissue  without  elastic  fibers.  The  inner 


HAIR 


393 


layer,  also  free  from  elastic  tissue,  is  sometimes  longitudinally  fibrous,  and 
sometimes  homogeneous.  It  forms  the  outer  stratum  of  the  hyaline  (or 
vitreous]  membrane,  and  is  continuous  below  with  the  thin  but  distinct 


Hair  cuticle.    Cortical  substance. 

i      1 

I       Medullary  substance. 
I     J        '  I 


Shaft  of  the  hair. 


Longitudinal  fiber 
layer. 


Circular  fiber  layer. 


Outer  layer  of  the  hya- 
line membrane. 


Inner  layer  of  the  hya- 
line membrane. 


Outer  epithelial  _ 
sheath. 


Henle's  layer.  - 
Huxley's  layer. 


Cuticle  of  the  inner  — 
sheath. 


Papilla.  . 


FIG.  399- — LONGITUDINAL  SECTION  OF  THE  LOWEST  PART  OF  THE  ROOT  OF  A  HAIR.   (From  a  section  of 

the  human  scalp.)      X  200. 
The  kerato-hyalin  granules  are  colored  red. 


394 


HISTOLOGY 


Cortex.  _ 


Medulla. 


layer  which  covers  the  papilla  (Fig.  399).  An  inner  stratum  of  the  hyaline 
membrane  is  formed,  according  to  Stohr,  from  the  epithelial  cells  of  the 
root  sheath.  This  inner  stratum  is  provided  with  fine  pores,  and  is 
always  clear  and  homogeneous.  It  may  unite  with  the  connective  tissue 
stratum  so  that  both  may  appear  as  a  single  membrane.  The  connective 
tissue  sheath  is  found  fully  developed  only  around  the  lower  half  of  the  root. 
The  outer  epithelial  sheath  is  an  inpocketing  of  the  epidermis.  The 
stratum  corneum  extends  to  the  sebaceous  gland;  the  stratum  granulosum 
continues  somewhat  deeper,  but  only  a  thinned  stratum  germinativum 
can  be  followed  to  the  bulb.  All  of  these  are  included  in  the  outer  epi- 
thelial sheath  (Figs.  401-405,  I,  II,  and  5). 

The  inner  epithelial  sheath  extends  from  the  sebaceous  gland  to  the  bulb. 
It  begins  as  a  layer  of  cornified  cells  below  the  termination  of  the  stratum 

granulosum,  but  it  is  not  a  continuation  of 
that  layer.  Toward  the  bulb  the  inner 
sheath  is  divisible  into  two  layers.  The 
outer  or  Henle's  layer  consists  of  one  or  two 
rows  of  cells  with  occasional  atrophic  nuclei; 
for  the  most  part  they  are  non-nucleated. 
The  inner  or  Huxley's  layer  is  a  row  of 
nucleated  cells.  The  inner  surface  of  Hux- 
ley's layer  is  covered  by  a  membrane,  the 
cuticula  of  the  sheath,  composed  of  non- 
nucleated  cornified  scales.  Traced  down- 
ward, the  elements  of  the  inner  epithelial 
sheath  and  its  cuticula  all  become  nucleated 
cells,  but  the  layers  may  be  distinguished 
almost  to  the  neck  of  the  papilla.  There 
they  lose  their  sharp  boundaries,  but  may 
still  be  distinguished  from  the  pigmented 
cells  of  the  bulb.  Traced  upward,  it  is 

found  that  kerato-hyalin  granules  appear  in  Henle's  layer  at  the  level  of  the 
papilla,  and  in  Huxley's  layer  somewhat  higher  (Fig.  399) ;  still  higher  these 
granules  disappear  and  the  cells  of  the  inner  sheath  become  cornified. 

The  shaft  of  the  hair  is  entirely  epithelial;  it  consists  of  cuticula, 
cortex  and  medulla  (Fig.  400).  The  cuticula,  which  covers  its  surface,  is  a 
thin  layer  formed  of  transparent  scales  directed  from  the  center  of  the  shaft 
outward  and  upward,  thus  overlapping  like  inverted  shingles.  This 
arrangement  is  readily  seen  in  wool  and  the  hairs  of  various  mammals,  but 
is  much  less  evident  in  human  hair.  The  cuticula  is  composed  of  non- 
nucleated  cornified  cells. 

The  greater  portion  of  the  shaft  is  included  in  the  cortex.  Toward  the 
bulb,  the  cortex  consists  of  soft  round  cells;  distally  these  cells  become  corni- 


Cuticula.  —^ 


FIG.  400.— PART  OF   A  WHITE  HUMAN 
HAIR.      X  240. 


HAIR 


395 


FIG.  402. 


FIG.  403. 


FIG.  402. 


Seb.' 
Musc.._ 


,B 
FIG.  403. 


£^r^^^'-rr^  - 

-^iv;.|^ 

x-  *'   <  .  JVA>  ft:.;.--.-  • 


.- 
^^<^m*i-  > 


Bulbus  pili.  •• 


Papilla. 


FIG  405. 

FIGS.  401-405. — FOUR  CROSS  SECTIONS  OF  A  HAIR  OF  THE  HEAD  (X  160),  WITH  A  DIAGRAMMATIC  LONGI- 
TUDINAL ViEWJiFOR  ORIENTATION. 

A,  Cuticula;  B,  cortex;  C,  medulla.  I,  Str.  corneum;  II,  str.  germinativum ;  III,  corium.  1-3,  Connective- 
tissue  sheath;  i,  longitudinal  fiber  layer;_  2,  circular  fiber  layer;  3,  conn.  tiss.  hyaline  membrane;  4, 
epithelial  hyaline  membrane;  5,  outer  epithelial  sheath;  6,  inner  epithelial  sheath;  6a,  Henle's  layer; 
6b,  Huxley's  layer;  7,  cuticula  of  the  sheath;  Muse.,  arrector  pili;  Seb.,  sebaceous  gland. 


396 


HISTOLOGY 


fied,  elongated  and  very  closely  joined  together.     Their  nuclei  are  then 
linear.     The  cortex  of  colored  hairs  contains  pigment  both  in  solution 

and  in  the  form  of  granules.      These 
A  R  r.  n 

granules  are  partly  within  the  cells, 
and  partly  between  them.  Moreover 
every  fully  developed  hair  contains 
minute  intercellular  air-spaces,  found 
within  both  cortex  and  medulla.  But 
a  medulla  is  lacking  in  many  hairs,  and 
when  present,  in  the  thicker  hairs,  it 
does  not  extend  their  whole  length.  It 
consists  of  cuboidal  cells  containing 
kerato-hyalin  (Fig.  399),  and  generally 
afranged  in  a  double  row.  Their  nu- 
clei are  degenerating. 
Growth  and  Replacement  of  Hairs.  The  growth  of  the  shaft,  and  of  the 
inner  epithelial  sheath  with  its  cuticula,  takes  place  through  continued 


Epithelial  bed. 

FIG.  406. — FOUR  STAGES  IN  THE  SHEDDING  OF 
A  HAIR.  FROM  THE  SKIN  OF  THE  NOSE 
OF  A  SEVEN  AND  ONE-HALF  MONTHS 
EMBRYO.  X  50. 

Parts  of  A  and  B  are  shown  enlarged  in  Figs. 
407  and  408. 


Remains  of  inner 
/  sheath. 


Iw 

Sft* 


Cornified 
•/  .     bulb. 


*.»« 


Jipitneu 

^^\N  s"       bed 


Remains  of  inner 
sheath. 

Cornified  bulb. 
Epithelial 


L%S» 


•WS 

«*%      ,;£*& 

<«r         .**) 
r^*I  "^li 

Thin  hyaline  __X^ 
membrane. 


Epithelial  cord 


"" 


Sf 


Thick  hyaline  _ 

membrane.    ~" 


Epithelial 
cord. 


Matrix  cells. 
Papilla. 


FIG.  407. — LOWER  PART  OF  FIG.  406,  A. 


Atrophic  papilla. 
Connective  tissue. 


FIG.  408.  —  LOWER  PART  OF  FIG.  406,  B.     X  230. 


mitotic  division  of  the  epithelial  matrix  cells  of  the  bulb  of  the  hair.  These 
become  cOrnified,  and  are  added  from  below  to  the  cells  previously  cor- 
nified.  Accordingly  the  oldest  cells  are  at  the  tip  of  the  hair  and  the  young- 


HAIR  397 

est  are  immediately  above  the  bulb.  The  outer  epithelial  sheath  grows  in 
a  radial  direction  from  the  inner  surface  of  the  hyaline  membrane  toward 
the  shaft. 

Shortly  before  and  after  birth,  there  is  a  general  shedding  of  hair,  sub- 
sequent to  which  the  loss  and  replacement  of  individual  hairs  is  constantly 
taking  place.  A  hair  of  the  scalp  is  said  to  last  1600  days,  but  the  duration 
of  other  hairs  has  not  been  definitely  determined.  The  process  of  removal 
begins  with  a  thickening  of  the  hyaline  membrane  and  circular  fiber 
sheath.  The  matrix  cells  cease  to  produce,  first  the  inner  epithelial  sheath, 
and  then  the  cuticulae  and  shaft.  The  hollow  bulb  becomes  a  solid  corni- 
fied  "club."  The  matrix  cells  increase  without  differentiating  into  hair 
cells  or  sheath  cells,  and  the  clubbed  hair,  with  its  inner  sheath,  is  forced 
outward  to  the  level  of  the  orifice  of  the  sebaceous  gland,  where  it  may 
remain  for  some  time  (Fig.  406,  D) .  The  lower  part  of  the  outer  epithelial 
sheath,  which  has  become  empty,  forms  an  epithelial  strand  which  shortens 
and  draws  the  papilla  upward;  but  the  connective  tissue  sheath  remains 
behind,  forming  the  "hair  stalk."  After  some  time,  the  columnar  cells 
of  the  epithelial  bed  proliferate,  causing  the  epithelial  cord  to  return  to  its 
former  depth  (Figs.  407  and  408),  and  a  new  hair  develops  in  the  old  sheath 
upon  the  old  papilla.  The  new  hair  in  growing  toward  the  surface  Com- 
pletes the  expulsion  of  its  predecessor,  which  is  dislodged  together  with 
cells  of  the  adjacent  epithelial  bed. 

SEBACEOUS  GLANDS. 

The  sebaceous  glands  are  simple,  branched  or  unbranched  alveolar 
structures  situated  in  the  superficial  layer  of  the  corium  and  usually  ap- 


Epidermis.  f  \j~A 

Cell  with  shrunken 
nucleus. 


Cell    with    well-devel- 

cerium. (  msmfixwm-  °»"S£.'*'m- 


ii    Cell  with  developing 
/        drops  of  secretion. 

Cuboidal  cell. 

Fig.  409. — A,  FROM  A  VERTICAL  SECTION  THROUGH  THE  ALA  NASI  OF  A  CHILD.  X  40.  C,  Stratum  cor- 
neum;  M,  stratum  germinativum ;  t,  sebaceous  gland  consisting  of  four  sacs,  a,  duct  of  the  same:  w, 
lanugo  hair,  about  to  be  shed;  h,  sheath  of  the  same,  at  the  base  of  which  a  new  hair,  x,  is  forming. 

B,  FROM  A  VERTICAL  SECTION  OF  THE  SKIN  or  THE  ALA  NASI  OF  AN  INFANT.  X  240.  Sac  of  a  sebaceous 
gland  containing  gland  cells  in  various  stages  of  secretion. 

pended  to  the  sheath  of  a  hair  (Fig.  398).     In  connection  with  the  lanugo, 
a  large  gland  may  be  associated  with  a  very  small  hair  (Fig.  409),  and  in 


398  HISTOLOGY 

exceptional  cases  as  at  the  margin  of  the  lip  or  on  the  labia  minor  a,  they 
occur  independently  of  hairs.  They  vary  in  size  from  0.2  to  2.2  mm.,  the 
largest  being  found  in  the  skin  of  the  nose  where  the  ducts  are  macro- 
scopic. None  are  found  in  the  palms  or  soles,  where  hairs  also  are  absent. 

The  short  duct  is  a  prolongation  of  the  outer  epithelial  sheath  of  the  hair 
and  is  formed  of  stratified  epithelium,  the  number  of  layers  of  which  de- 
creases toward  the  alveoli.  The  alveoli  consist  of  small  cuboidal  basal 
cells,  and  of  large  rounded  inner  cells  in  all  stages  of  fatty  metamorphosis. 
As  the  cell  becomes  full  of  vacuoles,  the  nucleus  degenerates,  and  the  cell 
is  cast  off  with  its  contained  secretion.  In  life  the  product  of  the  glands  is 
a  semi-fluid  material,  composed  of  fat  and  broken-down  cells. 

Glandules,  prceputiales  are  sebaceous  glands  without  hairs  which  are 
sometimes,  but  not  always,  found  on  the  glans  and  praeputium  penis. 
The  designation  "Tyson's  glands"  is  not  justified  since  Tyson  described 
the  epithelial  pockets  f  to  i  cm.  long  which  regularly  occur  near  the  fren- 
ulum  praeputii.  Praeputial  glands  and  crypts  are  not  found  in  the  embryo. 
The  praeputium  is  united  to  the  outer  surface  of  the  glans  by  an  epithelial 
mass,  which  often  persists  after  birth  and  is  broken  up  by  the  formation 
of  concentric  epithelial  pearls.  Glands  and  crypts  are  absent  from  the 
praeputium  and  glans  of  the  clitoris. 

SWEAT  GLANDS. 

The  glandulcB  sudoriparce  are  long  unbranched  tubes  terminating  in  a 
simple  coil  (described  by  Oliver  Wendell  Holmes  as  resembling  a  fairy's 
intestine,  Fig.  410).  The  coil  is  found  in  the  deep  part  of  the  corium  or 
in  the  subcutaneous  tissue  (Fig.  387).  The  duct  pursues  a  straight  or 

somewhat  tortuous  course  to  the  epidermis 
which  it  enters  between  the  connective  tissue 
papillae.  Within  the  epidermis  its  spiral  wind- 
ings are  pronounced  (Fig.  387);  it  ends  in  a 
pore  which  may  be  detected  macroscopically. 

The  epithelium  of  the  ducts  consists  of  two 
or  three  layers  of  cuboidal  cells;  it  has  an  inner 
cuticula,  and  an  outer  basement  membrane 
covered  by  longitudinal  connective  tissue  fibers. 

(Aft2rTHub?rLE  °  Within  the  epidermis  its  walls  are  made  of  cells 

of  the  strata  through  which  it  passes.      The 

secretory  portion  of  the  gland  (3.0  mm.  long  according  to  Huber)  forms 
about  three-fourths  of  the  coil,  the  duct  constituting  the  remainder.  The 
secretory  epithelium  is  a  simple  layer  of  cells,  varying  from  low  cuboidal 
to  columnar,  according  to  the  amount  of  secretion  which  they  contain. 
Those  filled  with  secretion  present  granules,  some  of  which  are  pigment  and 


SWEAT    GLANDS 


399 


fat.  The  product  is  eliminated  through  intra-  and  intercellular  secretory 
capillaries.  It  is  ordinarily  a  fatty  fluid  for  oiling  the  skin,  but  it  becomes 
the  watery  sweat  under  the  influence  of  the  nerves.  The  gland  cells  are 
not  destroyed  by  either  form  of  activity.  The  secretory  tubule  is  sur- 
rounded by  a  distinct  basement  membrane,  within  which  there  is  a?row 
of  small  longitudinally  elongated  cells  described  as  muscle  fibers.  They 
do  not  form  a  complete  membrane,  and  they  appear  as  a  continuation  of 
the  basal  layer  of  cells  of  the  ducts. 

Sweat  glands  are  distributed  over  the  entire  skin,  except  that^of  the 
glans  and  the  inner  layer  of  the  praeputium  penis.  They  are  most  numer- 
ous in  the  palms  and  soles.  In  the  axilla  there  are  branched  sweat  glands 
and  large  forms  with  30  mm.  of  coiled  tube.  They  acquire  their  large  size 
at  puberty  and  have  been  considered  as  sexual  "odoriferous"  glands.  In 
the  vicinity  of  the  anus  there  are  also  branched  sweat  glands,  together 
with  the  large  unbranched  "circum-anal  glands." 


A.  Duct  in 
cross  section. 


Nuclei  of 
gland  cells. 


Membrana  propria. 


Cuticula. 


Muscle  fibers. 


B.  Columnar  epithelium 
from  the  coiled  tubule. 


C.  Surface  view 
of  the  coiled  tubule. 


D.  Low  epithelium  from 

a  coiled  tubule. 

Membrana  propria. 

Muscle;.fibers. 

Muscle  nucleus. 
Cuticula. 

-  Membrana  propria. 
Muscle  fiber. 

E.  Cross  section  of 
coiled  tubule. 


FIG.  411. — A-D,  FROM  A  SECTION  OF  THE  SKIN  OF  THE  AXILLA;  E,  FROM  THE   FINGER  TIP  OF  A  MAN  OF 
TWENTY-THREE    YEARS.     X  230.     E    is    not    a    true    cross    section. 


VESSELS  AND  NERVES  OF  THE  SKIN. 

The  arteries  proceed  from  a  network  above  the  fascia,  and  branch  as 
they  ascend  toward  the  surface  of  the  skin.  Their  branches  anastomose, 
forming  a  cutaneous  plexus  in  the  lower  portion  of  the  corium.  From 
this  plexus  branches  extend  to  the  lobules  of  fat  and  to  the  coils  of  the 
sweat  glands,  about  which  they  form  "baskets"  of  capillaries.  Other 
branches  pass  to  the  superficial  part  of  the  corium. where  they  again  anas- 
tomose, forming  a  subpapillary  plexus,  before  sending  terminal  arteries 
into  the  papillae.  The  subpapillary  plexus  sends  branches  also  to  the 
sebaceous  glands  and  hair  sheaths,  but  the  papilla  of  a  hair  receives  an 
independent  artery.  The  veins  which  receive  the  blood  from  the  super- 
ficial capillaries  form  a  plexus  immediately  beneath  the  papillae,  and 
sometimes  another  just  below  the  first  and  connected  with  it.  The  veins 
from  these  plexuses  accompany  the  arteries  and  the  ducts  of  the  sweat 


400 


HISTOLOGY 


glands  to  the  deeper  part  of  the  corium,  where  they  branch  freely,  receiv- 
ing the  veins  from  the  fat  lobules  and  sweat  glands.  Larger  veins  con- 
tinue into  the  subcutaneous  tissue  where  the  main  channels  receive  specific 
names. 

The  lymphatics  form  a  fine- meshed  plexus  of  narrow  vessels  beneath 


Epidermis. 


Corium. 


Branches   of   the    subpapil- 
lary  arterial  plexus. 

Veins   of  the  second  super- 
ficial plexus. 


——Veins  along  the  duct  of 
sweat  gland. 


Subcutane- 
ous   tissue. 


Large  vein. 


Vessel  to  the  Vessel  to  the 

fat  tissue.  sweat  gland. 

FIG.  412.  —  PART  OF  A  VERTICAL  SECTION  OF  THE  INJECTED  SKIN  OF  THE  SOLE  OF  THE  FOOT.     X  20. 
The  veins  are  not  completely  filled  by  the  injection- 

the  subpapillary  network  of  blood  vessels,  receiving  tributary  loops  from 
the  papillae.  This  plexus  empties  into  a  wide-meshed  subcutaneous 
plexus.  There  are  lymphatic  vessels  around  the  hair  sheaths,  sebaceous 
glands,  and  sweat  glands. 

The  nerves  form  a  wide-meshed  plexus  in  the  deep  subcutaneous  tissue, 
and  secondary  plexuses  as  they  ascend  through  the  skin.    The  sympathetic, 


CUTANEOUS    NERVES 


4OI 


non-medullated  nerves  supply  the  numerous  vessels,  the  arrector  pili 
muscles,  and  the  sweat  glands;  an  epilamellar  plexus  outside  of  the  base- 
ment membrane  sends  branches  through  the  membrane  to  terminate 
in  contact  with  the  gland  cells.  Medulla  ted  sensory  nerves  end  in  the 
various  corpuscles  already  described,  and  in  free  terminations,  some 
being  intraepithelial.  Medullated  fibers  to  the  hairs  lose  their  myelin 
and  form  elongated  free  endings  with  terminal  enlargements  in  contact 
with  the  hyaline  membrane.  (The  nerves  to  the  tactile  hairs  of  some 
animals  penetrate  the  hyaline  membrane  and  terminate  in  tactile  menisci 
among  the  cells  of  the  outer  epithelial  sheath.)  Small,  round  or  discoid 
elevations  of  the  epidermis,  visible  with  the  naked  eye,  occur  close  to  the 
hairs  as  they  emerge  from  the  skin,  being  on  the  side  toward  which  the 
hairs  slope.  These  "hair  discs"  (Pinkus)  are  said  to  be  abundantly  sup- 
plied with  nerves.  The  corium  beneath  the  nails  is  rich  in  medullated 
nerves,  the  non-medullated  endings  of  which  enter  the  Golgi-Mazzoni 
type  of  lamellar  corpuscle  (having  a  large  core  and  few  lamellae),  or  they 
form  knots  which  are  without  capsules.  Elsewhere  the  skin  contains 
tactile  corpuscles  in  its  papillae  and  lamellar  corpuscles  in  the  subcutaneous 
tissue,  together  with  free  endings  in  the  corium  and  epidermis  (as  far  out 
as  the  stratum  granulosum). 

MAMMARY  GLANDS. 

In  young  mammalian  embryos  generally,  the  mammary  glands  are 
first  indicated  by  a  thickened  line  of  ectoderm  extending  from  the  axilla 
to  the  groin.  Later  much  of  the  line  disappears,  leaving  a  succession  of 
nodular  thickenings  corresponding  with  the  nipples.  In  some  mammals 


FIG.  413. — SECTION  THROUGH  THE  MAMMARY  GLAND  OF  AN  EMBRYO  OF  25  CM. 
i.   Connective  tissue  of  the  gland.     (After  Basch,   from   McMurrich.) 

this  row  of  nipples  remains,  in  others  only  the  inguinal  thickenings,  and 
in  still  others  only  those  toward  the  axilla.  Thus  in  man  there  is  normally 
only  one  nipple  on  each  side,  but  structures  interpreted  as  accessory  nipples 
are  frequent;  they  are  not  always  situated  along  the  mammary  line. 
In  an  embryo  of  25  cm.  (Fig.  413)  several  solid  cords  have  grown  out  from 
26 


4O2 


HISTOLOGY 


the  ectodermal  proliferation.  There  are  ultimately  from  15  to  20  of  these 
in  each  breast,  and  they  branch  as  they  extend  through  the  connective  tis- 
sue. At  birth  the  nipple  has  become  everted,  making  an  elevation,  and 
at  that  time  the  glands  in  either  sex  may  discharge  a  little  milky  secretion 
similar  to  the  colostrum  which  precedes  lactation.  The  glands  grow  in  both 
sexes  until  puberty,  when  those  in  the  male  atrophy  and  only  the  main 
ducts  persist.  In  the  female  enlarged  terminal  alveoli  are  scarcely  evi- 
dent until  pregnancy.  The  glands  until  then  are  discoid  masses  of  connec- 
tive tissue  and  fat  cells,  showing  in  sections  small  scattered  groups  of  duct- 
like  tubes. 

Toward  the  end  of  pregnancy  each  of  the  fifteen  or  twenty  branched 
glands  forms  a  mammary  lobe,  and  its  alveolo- tubular  end  pieces  are 

Branch  of  an  excretory  duct.         Connective  tissue. 


Alveolo-tubular 
end  piece. 


FIG.  414. — SECTION  OF  A  HUMAN  MAMMARY  GLAND  AT  THE  PERIOD  OF  LACTATION.     X  50. 

grouped  in  lobules.  The  secretory  epithelium  is  a  simple  cuboidal  or 
flattened  layer,  in  which  fat  accumulates  at  the  seventh  or  eight  month  of 
pregnancy.  The  fat  first  appears  as  small  granules  at  the  basal  ends  of 
"the  cells,  where  it  is  taken  up  from  the  surrounding  tissue.  It  is  not  pro- 
duced by  the  gland  cells.  Leucocytes,  derived  from  the  connective  tissue, 
make  their  way  between  the  epithelial  cells  of  the  alveoli  and  enter  the 
gland  lumen,  where  some  of  them  degenerate;  others  receive  fat  from  the 
gland  cells,  either  in  solution,  or  in  drops  which  are  devoured  by  phagocytic 
action.  These  fatty  leucocytes  grow  to  considerable  size  and  are  called 
colostrum  corpuscles.  Beneath  the  alveolar  epithelium  there  are  basal  or 
basket  cells,  which  have  been  compared  with  the  muscle  fibers  of  sweat 


MAMMARY    GLANDS 


403 


glands.     A  basement  membrane  separates  them  from  the  connective  tissue 
which  contains  many  lymphocytes  and  eosinophilic  cells. 

After  the  birth  of  the  child,  the  gland  cells  become  larger  and  are  filled 
with  stainable  secretory  granules  and  fat  droplets;  the  latter  are  near 
the  lumen  and  are  often  larger  than  the  nucleus  (Fig.  415).  After  two 
days  of  lactation,  some  of  the  gland  cells  are  flat 
and  empty  of  secretion.  Others  are  tall  and 
columnar,  with  a  rounded  border  toward  the 
lumen;  often  they  contain  two  nuclei.  The 
fat  within  them  is  not  the  result  of  degenera- 
tion as  in  sebaceous  glands,  nor  a  secretion  pro- 
duced by  the  nucleus;  it  accumulates  through 
protoplasmic  activity,  and  the  cell  may  be  filled 
several  times  before  it  perishes.  Transitions 
between  low  empty  cells  and  columnar  forms 
occur,  but  mitoses  are  absent  from  the  lactating  gland, 
sions  are  numerous  during  pregnancy. 

Milk  consists  of  fat  droplets,  2-5  /z  in  diameter,  floating  in  aiclear  fluid 
which  contains  nuclein  derived  from  degenerating  nuclei,  and  occasionally 
a  leucocyte  or  colostrum  corpuscle.  Free  nuclei  may  be  found,  and  some 
cells  which  undoubtedly  are  to  be  interpreted  as  detached  from  the  alveoli 
of  the  gland. 


Gland  cell.  Membrana  Oil  drops, 
propria. 

FIG.  415. — PROM  A  SECTION  OF 
THE  MAMMARY  GLAND  OF 3 A 
NURSING  WOMAN.  X  250. 


Mitotic  divi- 


?-.* 

o  o° 
o.'O 


FIG.  416. — A.,  MILK  GLOBULES  FROM 
HUMAN  MILK.  X  560.  B.,  ELE- 
MENTS OF  THE  COLOSTRUM  OF  A 
PREGNANT  WOMAN.  X  560. 

i,  Cell  containing  uncolored  fat  globu- 
les; 2,  cell  containing  minute 
colored  fat  globules;  3,  leucocyte; 
4,  milk  globules. 


2 


FIG.  417. — FROM  A  THICK  SECTION  OF  THE  MAM- 
MARY GLAND  OF  A  WOMAN  LAST  PREGNANT  Two 
YEARS  BEFORE.  X  50. 

i,  Large  excretory  duct;  2,  small  excretory  duct;  3, 
gland  lobules,  separated  from  one  another  by  con- 
nective tissue. 


At  the  end  of  lactation,  the  connective  tissue,  which  has  become  greatly 
reduced  owing  to  the  enlargement  of  the  glands,  increases  in  quantity  and 
the  leucocytes  reappear;  as  during  pregnancy,  they  form  colostrum  cor- 
puscles. The  lobules  become  smaller  and  the  alveoli  begin  to  degenerate. 


i 

404  HISTOLOGY 

In  old  persons  all  the  end  pieces  and  lobules  have  gone  and  only  the 
ducts  remain. 

The  ducts  are  lined  with  simple  columnar  epithelium,  surrounded  by  a 
basement  membrane  and  generally  by  circular  connective  tissue  bundles. 
Toward  the  nipple  each  duct  forms  a  considerable  spindle-shaped  dilata- 
tion, the  sinus  lactiferus.  The  epithelium  near  the  outlet  of  the  ducts 
is  stratified  and  squamous. 

The  skin  of  the  nipple,  and  of  the  areola  at  its  base,  contains  abundant 
pigment  in  the  deepest  layers  of  its  epidermis.  The  cbrium  forms  tall 
papillae  and  contains  smooth  muscle  fibers,  some  of  which  extend  vertically 
through  the  nipple  and  others  are  circularly  arranged  around  the  ducts. 
There  are  tactile  corpuscles  in  the  nipple,  and  lamellar  corpuscles  have  been 
found  beneath  its  areola.  It  is  particularly  sensitive,  and  upon  irritation 
becomes  rapidly  elevated,  due  both  to  muscular  and  vascular  activity. 
There  are  many  sweat  and  sebaceous  glands  in  the  areola,  and  occasional 
rudimentary  hairs.  The  areolar  glands  (of  Montgomery)  are  branched 
tubular  glands  having  a  lactiferous  sinus  and  otherwise  resembling  the 
constituent  mammary  glands.  Their  funnel-shaped  outlets  are  surrounded 
by  large  sebaceous  glands.  The  areolar  glands  are  regarded  as  transitions 
between  sweat  glands  and  mammary  glands. 

Blood  vessels  enter  the  breast  from  several  sources  and  form  capillaries 
around  the  alveoli.  Lymphatic  vessels  are  found  in  the  areola,  around 
the  sinuses,  and  in  the  interlobular  tissue.  The  collecting  lymphatics  pass 
chiefly  toward  the  axilla;  a  few  penetrate  the  intercostal  spaces  toward 
the  sternum.  The  nerves  are  mostly  those  which  supply  the  blood  vessels, 
but  fibers  are  said  to  extend  to  the  glandular  epithelium. 

SUPRARENAL  GLANDS. 

Development  and  General  Features.  The  suprarenal  glands  are  two 
flattened  masses  of  cells,  without  lumen  or  ducts,  situated  in  the  retroperi- 
toneal  tissue  above  the  kidneys.  They  vary  considerably  in  size  and 
shape,  but  are  usually  about  a  quarter  of  an  inch  thick  and  between  i  and 
2  inches  tall,  sometimes  being  wider  and  sometimes  narrower  than  their 
height.  '  The  right  suprarenal  gland  is  generally  described  as  triangular 
and  the  left  as  crescentic. 

The  gland  resting  upon  the  kidney  (Glandula  Reni  incumbens]  was  first  described 
by  Eustachius  (Tractatio  de  Renibus,  1564).  It  was  apparent  from  the  outset  that 
the  relation  of  the  suprarenal  glands  to  the  kidneys  was  merely  that  of  juxtaposition, 
nevertheless  most  anatomists  still  find  it  convenient  to  describe  them  with  the  urinary 
organs.  Certain  early  writers  supposed  that  they  were  renal  structures  and  named 
them  "succenturiate  kidneys."  Bartholin  (Anatomia,  1666)  perceived  the  medulla, 
which  he  described  as  a  cavity  containing  a  black  humor;  and  he  published  an  extraor- 
dinary figure  in  which  the  gland  resembles  a  cocoanut  cut  across  with  the  lid  lifted. 


SUPRARENAL    GLANDS  405 

In  accordance  with  this  conception  he  named  the  structures  "atrobiliary  capsules," 
and  the  name  capsule  is  still  often  applied  to  them.  Diemerbroeck  (Anatome,  1672), 
following  Wharton,  states  that  "the  glands  are  found  at  a  place  where  there  is  a 
plexus  of  nerves,  to  which  they  are  firmly  united."  In  reviewing  the  various  "con- 
jectures" as  to  their  function,  he  writes,  "Wharton  thinks  that  in  these  capsules  a 
certain  juice  is  removed  from  the  plexus  of  nerves  on  whch  they  lie,  useless  indeed  to 
the  nervous  system,  but  which,  flowing  thence  into  the  veins,  may  serve  some  useful 
purpose."  The  intimate  relation  of  these  glands  to  the  nervous  system,  and  the 
production  of  an  internal  secretion  received  by  the  veins,  have  since  been  demon- 
strated; in  certain  recent  works  the  glands  have  even  been  described  as  parts  of  the 
nervous  system.  Diemerbroeck  concludes  by  hoping  that  physicians,  through 
many  autopsies,  may  find  out  to  what  diseases  these  glands  give  rise.  In  1855, 
Addison  described  the  disease,  usually  fatal,  which  is  thought  to  depend  upon  the 
loss  of  function  of  these  glands.  Their  physiological  importance  has  been  amply 
demonstrated,  but  they  still  present  fundamental  problems,  both  as  to  function  and 
structure. 

A  section  through  a  fresh  suprarenal  gland  reveals  at  once  the  division 
into  cortex  and  medulla.     The  cortex  is  yellowish,  owing  to  the  presence 
of  lipoid  substance,  and  the  medulla  is  dark  brown,  due  in  part  to  the  large 
amount  of  blood  which  it  contains.     The  color  con- 
trast is  usually  very  striking,  and  it  is  shown  also 
in  unstained  sections  of  tissue  preserved  in  chromic 
acid  solutions  (Fig.  418),  although  the  medulla  may 
then  be  lighter  than  the  cortex.     Not  only  do  the 
cortex  and  medulla  differ  in  gross  appearance,  but 
they  are  radically  different  in  embryonic  origin,  and 
in  the  sharks  they  exist  as  separate  organs.     In  sharks 
the  medulla  is  represented  by  groups  of  chromamn 
cells  associated  with  the  sympathetic  ganglia,  and  the 
cortex   takes   the  form  of   an    "interrenal   gland," 
composed  of  cords  of  mesodermal  cells  with  a  sinu- 

rjV-j          l    4.'  T       T_  1.  Cortex.        Medulla. 

soidal  circulation.     In  human  embryos  correspond-     FIG.  4i8.— SECTION  OF  THE 

.    ,       ,          , ,  , ,  SUPRARENAL  GLAND  OF 

ing  parts  arise  separately,  but  they  come  together  to         A  CHILD,    x  is. 
form  a  single  gland. 

The  cortex  appears  first,  and  is  formed  from  cells  which  develop  as  buds 
of  the  ccelomic  epithelium,  growing  into  the  mesenchyma  on  either  side  of 
the  root  of  the  mesentery,  medial  to  the  WolfEan  bodies.  In  embryos  of 
8-12  mm.,  the  buds  or  cords  have  become  detached  from  the  peritoneal 
epithelium  (Zuckerkandl),  and  in  cross  sections  they  appear  as  round 
masses  of  cells  penetrated  by  a  network  of  slender  veins.  The  cells 
of  these  masses  rest  directly  against  the  vascular  endothelium,  so  that 
the  vessels  are  described  as  sinusoids. 

Meanwhile  cells  from  the  sympathetic  ganglia  grow  ventrally  along 
the  medial  side  of  these  masses,  where  they  are  conspicuous  because  of 
their  dark  stain  (Fig.  419).  These  cells,  which  give  rise  to  the  medulla  of 


406 


HISTOLOGY 


S.B. 


the  suprarenal  gland,  do  not  appear  like  nerve  cells  and  may  be  radically 
different  from  them,  although  always  closely  associated  with  the  sympa- 
thetic ganglia.  Because  of  their  affinity  for  chromium  they  are  known 
as  chromaffin  cells.  They  produce  the  important  internal  secretion, 
adrenalin,  which  on  injection  causes  contraction  of  the  musculature  of 
the  blood  vessels,  with  consequent  rise  in  blood  pressure.  The  chromaffin 
cells  are  not  confined  to  the  suprarenal  glands,  as  already  stated  (p.  152). 
In  embryos  of  15-20  mm.,  strands  of  chromaffin  cells  are  seen  penetrating 
the  cortical  portion  of  the  gland,  but  it  is  not  until  much  later  that  they 
gather  in  a  central  mass  which  constitutes  the  medulla;  even  at  190  mm. 

the  invasion  is  not  complete 
(Zuckerkandl) .  As  a  whole,  the 
gland  acquires  a  relatively  very 
great  size  in  embryos. 

;jytS  From  this  mode  of  development, 

it  is  seen  that  islands  of  medullary 
substance  may  occasionally  occur  in 
the  cortex,  and  that  outlying  por- 
tions of  the  gland  may  not  contain 
any  medulla.  Moreover  portions  of 
the  gland  frequently  become  de- 
tached, forming  accessory  suprarenal 
glands.  These  may  remain  near  the 
main  glands  or  may  be  carried  down, 
with  the  descent  of  the  adjacent 
sexual  glands,  into  the  broad  liga- 
ment, or  epididymis  (cf .  Wiesel,  Sitzb. 
kais.  Akad.  Wiss.,  Wien,  1899,  vol. 
108,  pp.  257—280).  Such  glands  usually  consist  entirely  of  cortex,  but  they  may 
contain  medullary  substance.  Isolated  paraganglia,  consisting  entirely  of  medullary 
substance,  are  not  regarded  as  suprarenal  glands.  There  is  no  evidence  that  acces- 
sory suprarenal  glands  may  arise  from  the  coelomic  epithelium  at  a  distance  from  the 
main  glands  (Zuckerkandl,  Keibel  and  Mall's  Human  Embryology,  vol.  2). 

Adult  Structure.  The  cortical  substance  may  be  divided  into  three 
layers  or  zones — the  zona  glomerulosa,  zona  fasciculata,  and  zona  reticularis 
(Fig.  420).  The  zona  glomerulosa,  found  just  beneath  the  capsule,  is 
said  to  develop  between  the  second  and  third  years  after  birth,  "  reaching 
its  characteristic  structure  only  in  the  later  years  of  childhood."  It  con- 
sists of  round  masses  of  cells  which  in  man  are  much  like  those  of  the  zona 
fasciculata;  in  some  animals  they  are  distinguished  by  their  columnar  shape. 
The  zona  fasciculata  is  composed  of  cords  of  rounded  or  cuboidal  cells, 
containing  secretory  granules  and  an  abundance  of  fat  vacuoles  (Fig.  421). 
There  is  no  lumen  within  these  cords  and  they  are  not  surrounded  by  base- 
ment membranes.  Thin-walled  vessels  pass  between  them,  sometimes 
lodged  in  connective  tissue  strands'  proceeding  from  the  capsule.  The 


FIG.  419. — SECTION  OF  THE  SUPRARENAL  GLAND  OF  AN 
EMBRYO  OF  17  MM.  (Wiesel.) 

A,  Aorta;  R,  cortical  portion;  S,  chromaffin  tissue, 
penetrating  to  form  the  medulla  at  SB.  (From 
McMurrich's  Development  of  the  Human  Body.) 


SUPRARENAL   GLANDS 


407 


cords  of  the  zona  fasciculata  are  perpendicular  to  the  surface;  they  end 
below  in  a  network,  the  zona  reticularis.     In  this  deeper  portion  the  cells 


Zona  glomerulosa- 


Zona  fasciculata. 


Zona  reticularis.   — 


Cell  cords  of  the  medulla.     * 


Nerve  in  cross  section. 
Ganglion  cells. 

Bundles     of     smooth    muscle 
fibers  in  cross  section. 

Veins. 


Capsule. 


)    Cortex. 


Medulla. 


FIG.  420. — SECTION  OF  A  HUMAN  SUPRARENAL  GLAND,     x  so. 

become  pigmented,  so  as  to  form  a  dark  brown  band  visible  without 
magnification.     Fat  vacuoles  are  here  smaller  or  absent,  as  seen  in  Fig. 
421,  which  shows  also  the  close 
relation  between  the  cells  and 
the  vascular   endothelium.     In 
portions  of  the  suprarenal  gland 
where  the   medulla  is   lacking, 
the  zonae  reticulares  of  the  op- 
posite sides  come  together,  form- 
ing the  core  of  the  organ. 

The  medulla  is  composed  of 
chromamn  cells  arranged  in 
strands  and  masses  which  unite 
to  form  a  network,  with  lacunar 
veins  filling  the  interstices  (Fig. 
420).  The  cells  contain  an 
abundant  granular  protoplasm, 
but  they  tend  to  shrink,  even  in 
well-preserved  specimens,  so 
that  they  appear  stellate  (Fig. 


Blood 
vessels. 


Pigmented 
cells. 

Cells  of 

the  zona 

reticularis. 


Cell  of  the 
medulla. 


FIG.  421. — FROM  A  SECTION  OF  THE  SUPRARENAL  GLAND 
OF  AN  ADULT.     X  360. 


408 


HISTOLOGY 


Artery. 


Long  mefshed 
capillary  net  of 
the  cortex. 


421).     These  are  the  cells  which  are  believed  to  produce  adrenalin;  the 
function  of  the  cortical  cells  remains  unknown. 

The  capsule  of  the  suprarenal  glands  is  a  connective  tissue  layer,  said 
to  contain  smooth  muscle  fibers  and  small  ganglia,  in  addition  to  vessels  and 
nerves.  Around  the  blood  vessels  especially,  it  contains  elastic  tissue. 
The  capsule  sends  slender  prolongations  into  the  gland,  and  elastic  tissue 
occurs  in  the  medulla.  The  cortex  contains  very  few  if  any  elastic  fibers, 
and  its  framework  appears  to  consist  of  reticular  tissue. 

The  arteries  supplying  the  suprarenal  glands  are  from  several  sources. 
They  divide  into  many  small  branches  in  the  capsule,  and  these  penetrate 
the  cortex,  forming  a  long- meshed  capillary  network  (Fig.  422).  In  the 

medulla  the  meshes  be- 
come round  and  the 
vessels  collect  to  form 
veins,  the  larger  of  which 
are  accompanied  by  lon- 
gitudinal strands  of 
smooth  muscle  fibers. 
Some  arteries  are  said  to 
pass  directly  from  the 
capsule  to  the  medulla, 
without  branching  in  the 
cortex.  Within  the  med- 
ulla the  veins  unite  to 
form  the  central  veins, 
which  are  the  main  stems 
of  the  suprarenal  veins 
(Fig.  i68,p.  173).  They 
emerge  at  the  hilus;  the  right  empties  into  the  inferior  vena  cava  and  the 
left  joins  the  left  renal  vein. 

Lymphatic  vessels  have  been  found  in  the  capsule,  where  they  may 
drain  the  cortex,  and  also  in  the  medulla,  emerging  at  the  hilus. 

The  numerous,  mostly  non-medullated  nerves,  of  which  a  human 
suprarenal  gland  receives  about  thirty  small  bundles,  proceed  chiefly  from 
the  cceliac  plexus  and  pass  with  the  arteries  from  the  capsule  into  the  med- 
ulla. Within  the  capsule  they  form  a  plexus,  from  which  branches  de- 
scend into  the  zona  glomerulosa  and  zona  fasciculata;  there  they  end  on  the 
surface  of  groups  of  epithelioid  cells,  without  penetrating  between  the  in- 
dividual cells.  The  plexus  in  the  zona  reticularis  is  more  abundant,  and  is 
formed  from  fibers  which  descend  directly  through  the  outer  zones;  its 
fibers  likewise  terminate  on  the  ou.ter  surface  of  groups  of  cells.  In  the 
medulla,  the  nerves  are  extraordinarily  abundant  and  each  cell  is  sur- 
rounded by  nerve  fibers.  Groups  of  sympathetic  ganglion  cells  are  found 


Round  meshed 
net  of  the 
medulla. 


Vein  of  the 

medulla. 

FIG.  422. — FROM  A  SECTION  OF  AN  INJECTED  SUPRARENAL  GLAND  OF 
A  CHILD.     X  so. 


SUPRARENAL    GLANDS 


here  and  there  in  the  medulla  but  only  rarely  in  the  cortex, 
nerves  terminate  in  the  walls  of  the  vessels. 


409 
A  part  of  the 


CENTRAL  NERVOUS  SYSTEM. 

SPINAL  CORD. 

Development  and  General  Features.  The  formation  of  the  medullary 
tube,  which  gives  rise  to  the  spinal  cord  and  brain,  has  already  been  de- 
scribed (cf.  Fig.  125,  p.  133);  in  the  following  section,  the  differentia- 
tion which  takes  place  in  its  wall  will  be  considered,  together  with  the 
general  features  of  the  spinal  cord  in  the  adult. 

Very  early  in  development,  the  cells  of  the  medullary  tube  form  a 
syncytium.  Those  nuclei  of  the  syncytium  which  border  upon  the  lumen 


FIG.  423. — DIAGRAMS  SHOWING  THE  DIFFERENTIATION  OF  THE  CELLS  IN  THE  WALL  OF  THE  MEDULLARY 

TUBE.     (Schaper.) 

The  germinal  cells  are  stippled,  and  the  indifferent  cells  are  empty  circles.     Circles  with  dots  represent 
neuroglia  cells,  and  the  black  cells  are  neuroblasts.     Circles  containing  an  x  are  germinal  cells  in  mitosis. 

of  the  tube,  or  central  canal,  divide  repeatedly  by  mitosis,  and  many  of 
them  are  forced  outward  laterally,  so  that  the  sides  of  the  tube  become 
greatly  thickened.  In  the  floor  and  roof  of  the  tube  a  corresponding  thick- 
ening fails  to  take  place,  as  shown  in  Fig.  423. 

The  lateral  walls  of  the  tube  very  early  become  divisible  into  three 
layers  (Fig.  423).  The  inner  layer  consists  of  germinal  or.  proliferating 
cells  and  is  wide  only  in  the  embryo.  In  the  adult  it  becomes  reduced 
to  a  single  layer  of  inactive  cells,  which  surround  the  central  canal  like 
a  simple  epithelium  and  constitute  the  ependyma  (Gr.,  erreVSv/Aa,  a  cloak). 
The  middle  layer  is  composed  of  cells  derived  from  the  germinal  layer,  and 
in  the  adult  it  constitutes  the  gray  substance  of  the  cord.  Its  cells  early 
differentiate  into  two  types — the  supporting  cells,  or  neuroglia,  and  the 


410  HISTOLOGY 

nerve  cells.  The  processes  of  the  nerve  cells,  in  so  far  as  they  are  within 
the  limits  of  the  gray  substance,  are  non-medullated.  The  outer  layer  is 
at  first  entirely  free  from  nuclei,  and  later  it  contains  only  a  few  cell 
bodies,  belonging  with  the  neuroglia  and  with  the  endothelium  of  vessels 
which  penetrate  the  cord;  it  contains  no  nerve  cells.  This  layer  consists 
of  a  network  of  neuroglia  fibers  through  which  nerve  fibers  extend  in  vari- 
ous directions,  but  chiefly  up  and  down  the  cord.  As  these  fibers  become 
medullated,  the  layer  becomes  white  microscopically,  and  it  forms  the 
white  substance  of  the  adult  cord.  In  preparations  in  which  myelin  is 

Dorsal  Median ]   Portion  of 

Entrance     median         Dorsal  \      dorsal 

zone.        septum,      funiculus     j         Lateral  J       root.  Dorsal  root. 


mem 
bra 


~— — -Lateral 
funicult 


Dorso-  f' 
lateral, 

and  / 

Ventro-medial, 


Groups^of  nerve  cells. 


Central  canal. 


Ventral  root.  White  Ventral      Ventral  funiculus. 

commissure.       median 
fissure. 
FIG.  424.  —  CROSS  SECTION  OF  THE  LUMBAR  ENLARGEMENT  OF  THE  HUMAN  SPINAL  CORO.     X8. 

deeply  stained,  the  white  substance  appears  darker  than  the  gray  sub- 
stance (Fig.  424).  From  what  has  been  said,  it  appears  that  the  med- 
ullary tube  early  becomes  divisible  into  inner,  middle,  and  outer 
layers,  which  give  rise  to  ependyma,  gray  substance  and  white  substance 
respectively. 

As  the  medullary  tube  enlarges,  ventral  swellings  are  formed  on  either 
side  of  the  median  line  (Fig.  423).  These  later  project  so  far  ventrally 
that  the  floor  of  the  medullary  tube  is  found  at  the  dorsal  end  of  a  ventral 


SPINAL   CORD  411 

median  fissure,  which  is  bounded  on  either  side  by  the  bulgings  just  de- 
scribed. Into  each  of  these  two  swellings  the  gray  substance  projects, 
forming  the  ventral  " horns"  or  columns  (columna  anterior  or  ventralis). 
The  term  "horn"  refers  to  the  appearance  in  sections,  and  "column" 
applies  to  their  true  form,  taken  as  a  whole.  Corresponding  with  the 
ventral  columns  of  gray  substance,  there  are  two  dorsal  columns,  which 
arise  somewhat  later,  and  cause  the  gray  substance,  as  seen  in  sections, 
to  assume  the  form  of  a  letter  H.  With  many  variations  this  appearance 
is  characteristic  of  the  entire  spinal  cord  in  mammals  generally.  As 
seen  in  Fig.  424,  there  are  secondary  swellings  on  the  sides  of  the  "H" 
which  are  called  lateral  columns;  at  certain  levels  they  are  ill-defined  or 
absent. 

Instead  of  forming  a  dorsal  median  fissure,  the  medullary  tube  pro- 
duces a  dorsal  median  septum.  The  lower  or  ventral  part  of  the  septum 
is  apparently  formed  by  the  coalescence  of  the  lateral  walls  of  the  medul- 
lary tube,  thus  leaving  the  ventral  portion  of  the  original  lumen  as  the 
central  canal  of  the  adult.  Occasionally  this  small  cavity,  0.5-1.0  mm. 
wide,  is  entirely  obliterated.  The  dorsal  portion  of  the  septum  consists 
of  neuroglia  fibers  extending  from  the  roof  of  the  central  canal  to  the  per- 
iphery of  the  cord.  Thus  in  the  adult  the  cord  is  divided  into  right  and 
left  halves,  except  for  the  transverse  connections  or  commissures  near  the 
central  canal.  These  include  a  dorsal  commissure,  a  ventral  gray  commis- 
sure, and  a  ventral  white  commissure. 

The  white  substance  of  each  half  of  the  cord  is  subdivided  into  three 
longitudinal  funiculi,  each  of  which  includes  several  smaller  bundles  or 
fasciculi,  otherwise  known  as  "fiber -tracts."  The  funiculi  are  dorsal, 
lateral,  and  ventral  respectively,  and  their  boundaries  are  seen  without 
magnification.  The  dorsal  or  sensory  roots  enter  the  cord  along  a  groove 
known  as  the  dorso-lateral  sulcus,  and  the  ventral  or  motor  roots  emerge 
along  the  ventro-lateral  sulcus.  All  the  white  substance  between  these 
two  sulci  is  included  in  the  lateral  funiculus.  The  dorsal  funiculus  ex- 
tends from  the  dorso-lateral  sulcus  to  the  median  dorsal  septum;  and  the 
ventral  funiculus  extends  from  the  ventro-lateral  sulcus  to  the  mid- 
ventral  fissure. 

The  fasciculi  of  which  each  funiculus  is  composed  cannot  be  studied 
profitably  in  normal  specimens.  They  have  been  followed  chiefly  by 
observing  the  effects  of  local  injury  and  disease,  for  if  a  group  of  nerve  cells 
is  destroyed,  all  the  fibers  proceeding  from  it  will  degenerate.  In  this 
way  it  has  been  shown  that  the  fibers  of  the  funiculi  are  not  arranged  in- 
discriminately, but  occur  in  definite  tracts,  which  in  some  respects  are 
radically  different  in  different  animals.  Thus  the  fibers  of  voluntary 
motion  which  descend  from  the  cerebral  hemispheres  to  the  motor  cells  of 
the  cord,  forming  the  cerebro-spinal  fasciculi,  are  found  in  the  dorsal  fun- 


412  HISTOLOGY 

iculi  of  rodents  but  in  the  lateral  and  ventral  funiculi  of  the  human  cord. 
In  man  most  of  these  fibers,  in  descending  from  the  brain,  cross  to  the 
opposite  side  in  the  medulla  oblongata  and  complete  their  descent  in  the 
lateral  funiculus  of  the  cord,  where  they  form  the  lateral  cerebro-spinal 
fasciculus;  they  terminate  in  relation  with  motor  cells  on  the  same  side 
of  the  cord.  A  smaller  number  of  these  fibers  fail  to  cross  in  the  medulla, 
and  descend  in  the  ventral  funiculus  as  the  ventral  cerebro-spinal  fascicu- 
lus; these  fibers  cross  to  the  opposite  side  in  the  cord,  passing  through 
the  ventral  commissure,  and  then  terminate  in  relation  with  the  motor 
cells.  Thus  the  cerebro-spinal  fibers  all  cross,  but  the  decussation  may 
take  place  either  in  the  medulla  or  in  the  cord. 

The  fibers  which  convey  tactile  stimuli  to  the  brain  enter  by  the 
dorsal  roots  and  pass  into  the  gray  substance  of  the  cord,  where  they 
terminate  in  relation  with  small  cells  dorsally  placed.  Fibers  from  these 
cells,  cross  to  the  opposite  side  of  the  cord  through  the  gray  commissure, 
and  then  enter  the  white  substance  of  the  lateral  funiculus  in  which  they 
ascend  to  the  brain.  One  of  these  fibers  and  a  descending  fiber  of  the 
lateral  cerebro-spinal  fasciculus  are  shown  in  the  diagram,  Fig.  123,  p.  131. 

In  addition  to  fibers  of  the  long  tracts,  such  as  pass  between  the  spinal 
cord  and  the  hemispheres,  cerebellum  and  other  parts  of  the  brain,  the 
ventral  and  lateral  funiculi  contain  fibers  which  emerge  from  the  gray 
substance  of  the  cord  at  one  level  and  re-enter  it  at  another,  thus  placing 
the  cells  at  different  levels  in  communication.  The  fibers  of  these  "  ground 
bundles"  or  fasciculi  proprii  generally  remain  close  to  the  gray  substance. 
Their  entrance  and  exit  along  the  lateral  concavity  of  the  gray  substance 
causes  it  to  be  broken  up  into  zformatio  reticularis  (Fig.  424). 

The  dorsal  funiculi  in  the  upper  part  of  the  cord  are  each  subdivided 
into  a  slender  medial  fasciculus  gracilis  (column  of  Goll)  and  a  wider 
lateral  fasciculus  cuneatus  (column  of  Burdach),  which  are  partially  sepa- 
rated from  one  another  by  a  septum.  These  fasciculi  are  composed 
chiefly  of  the  fibers  of  "muscle  sense,"  which  enter  by  the  dorsal  roots 
and  divide  into  ascending  and  descending  branches.  Many  of  these  pass 
into  the  gray  substance  of  the  cord  after  traveling  varying  distances  in 
the  dorsal  funiculi.  Some  of  the  ascending  fibers,  however,  are  very  long 
and  extend  to  the  medulla  oblongata,  gradually  approaching  the  median 
septum  in  their  ascent.  The  gracile  fasciculi  are  composed  of  these  long 
ascending  fibers,  and  since  they  are  not  segregated  in  a  distinct  bundle  in 
the  lower  portion  of  the  cord,  this  fasciculus  is  absent  from  the  lumbar 
region.  In  addition  to  the  fibers  of  muscle  sense,  the  dorsal  funiculi  con- 
tain some  fibers  of  general  sensation,  a  limited  number  of  association 
fibers,  and  others. 

The  description  of  the  fiber  tracts  in  the  spinal  cord  and  brain  is  the 
subject  of  special  text-books;  they  are  briefly  and  clearly  described  by 


SPINAL   CORD  413 

Villiger  (Brain  and  Spinal  Cord,  translated  by  Piersol,  1912).  The  form 
of  the  cord  at  different  levels  is  considered  in  works  on  gross  anatomy. 
In  general,  the  white  substance  increases  toward  the  brain,  since  the 
cervical  cord  contains  the  fibers  to  and  from  all  the  lower  levels  in  addi- 
tion to  those  for  the  cervical  region  itself.  In  levels,  which  supply  the 
nerves  to  the  upper  and  lower  limbs,  there  is  a  general  increase  in  both 
gray  and  white  substances,  producing  the  cervical  and  lumbar  enlarge- 
ments, respectively.  The  lower  end  of  the  cord  tapers  into  the  rudimen- 
tary filum  terminale. 

Adult  Structure.  The  spinal  cord  and  brain  are  surrounded  by  two 
membranes  or  meninges,  of  which  the  outer  is  dense  and  fibrous,  and  is 
known  as  the  dura  mater;  and  the  inner  is  thin  and  vascular,  forming  the 
pi  a  mater. 

Curiously  they  are  not  called  membranes,  and  the  term  meninx  (in  the  singular)  is 
not  employed  in  anatomy.  They  retain  the  ancient  Arabic  designation  of  "mother  of 
the  brain,"  following,  according  to  Hyrtl,  a  general  Arabian  tendency  to  name  things 
"mothers,"  "fathers,"  etc.  (The  vena  cava  was  the  mater  venorum,  and  the  pupil,  the 
filia  oculi.)  Carrying  the  figure  further,  the  adjectives  of  double  meaning,  dura  and 
pia,  were  substituted  for  dense  and  thin.  In  the  fifteenth  century  it  was  said  that 
these  membranes  were  called  matres  because  they  produce  the  membranes  surrounding 
the  nerves,  the  coats  of  the  eye,  and  the  periosteum  of  the  skull,  with  which  they 
are  continuous;  but  Hyrtl  denies  that  the  term  has  any  such  significance. 

The  dura  mater  spinalis,  or  dura  mater  of  the  cord,  consists  of  compact 
fibrous  connective  tissue  with  many  elastic  fibers,  flat  connective  tissue 
cells  and  plasma  cells.  Its  inner  surface  is  covered  by  a  layer  of  flat  cells 
forming  a  mesenchymal  epithelium.  It  has  few  nerves  and  blood  vessels. 
Anteriorly  it  is  continuous  with  the  dura  mater  of  the  brain  at  the  foramen 
magnum.  It  does  not  fill  the  vertebral  canal,  and  is  not  continuous  with 
the  vertebral  periosteum.  Around  it  externally  there  is  a  layer  of  vascular 
fatty  connective  tissue;  and  internal  to  it  there  is  a  capillary  cleft  con- 
taining a  very  small  amount  of  fluid.  This  subdural  space  connects  with 
tissue  spaces  in  the  dura  and  with  those  which  extend  out  in  the  peri- 
neurium  of  the  peripheral  nerves.  •  It  communicates  freely,  but  probably 
indirectly,  with  the  lymphatic  vessels. 

The  pia  mater  spinalis,  as  described  by  Stohr,  is  a  two-layered  sac. 
The  outer  layer  is  covered  on  its  free  outer  surface  with  a  simple  layer  of 
flat  cells,  which  is  lightly  connected  with  the  dura,  and  forms  the  inner 
wall  of  the  subdural  space.  The  inner  layer,  or  pia  proper,  is  a  delicate 
and  very  vascular  connective  tissue,  closely  connected  with  the  spinal 
cord,  into  which  it  sends  prolongations  accompanying  the  blood  vessels. 
The  arteries  of  the  spinal  cord  are  primarily  two  pairs,  situated  as  shown 
in  Fig.  125,  E  (p.  133)  and  in  Fig.  424.  One  pair  is  ventral  to  the  dorsal 
roots,  and  the  other  is  near  the  mid-ventral  fissure;  their  branches  supply 
both  the  white  and  gray  substance,  and  the  collecting  veins  branch  freely 


414 


HISTOLOGY 


White 
substance. 


External  limiting 
membrane. 


in  the  pia  mater.  Between  the  two  layers  of  the  pia,  as  described  by  Stohr, 
there  is  a  wide  space  filled  with  cerebro-spinal  fluid  and  traversed  by  many 
strands  and  membranes  which  pass  from  one  layer  of  the  pia  to  the  other. 
These  strands  constitute  the  .arachnoid  membrane,  so-called  from  its 
cobwebby  texture.  Often  the  name  is  restricted  to  the  subdural  mem- 
brane (following  Henle),  so  that  the  spaces  between  the  meshes  of  the 
arachnoid  are  described  as  subarachnoid.  They  are  preferably  termed 
arachnoid  spaces  and  they  are  of  great  importance.  The  fluid  which  they 
contain  has  access  to  that  within  the  central  canal  of  the  cord  and  the 
ventricles  of  the  brain,  through  an  aperture  in  the  thin  roof  of  the  medulla 

oblongata.  Whether  the  arach- 
noid spaces  open  directly  into 
lymphatic  vessels  may  be  ques- 
tioned, but  undoubtedly  they  are 
freely  drained  by  the  lymphatic 
system. 

On  either  side  of  the  cord,  be- 
tween the  successive  spinal  nerves, 
there  is  a  frontally  placed  tri- 
angular plate  of  fibrous  connective 
tissue,  which  passes  from  the  pia 
to  the  dura  and  serves  to  support 
the  cord.  The  succession  of  these 
pointed  projections,  with  their 
bases  attached  to  the  pia,  consti- 
tutes the  denticulate  ligament. 

White  Substance.  The  white 
substance  of  the  cord  consists  es- 
sentially of  medullated  nerve  fibers 
supported  by  a  network  of  neu- 

roglia.  Toward  the  outer  surface,  the  neuroglia  fibers  become  felted  to- 
gether, forming  an  external  limiting  membrane  just  within  the  pia  mater 
(Fig.  425);  this  is  an  ectodermal  tissue,  which  must  be  distinguished 
from  the  adjacent  connective  tissue  penetrating  the  cord  with  the  blood 
vessels.  Although  in  transverse  sections  the  neuroglia  fibers  appear  to 
be  radially  arranged  (Fig.  425),  longitudinal  sections  show  that  they  ex- 
tend also  up  and  down  the  cord  (Fig.  426),  and  in  fact  they  form  a  dif- 
fuse syncytial  network.  The  protoplasm  of  this  network  is  characterized 
by  the  presence  of  stiff  neuroglia  fibrils,  'imbedded  in  the  peripheral 
exoplasm,  and  passing  freely  from  one  cell  territory  to  another.  They  are 
well  shown  in  specimens  stained  with  Mallory's  phosphotungstic  acid 
haematoxylin,  and  resemble  the  myoglia  and  fibroglia  fibrils  both  in  form 
and  staining  reaction. 


Cross  sections  of 
medullated 
nerve  fibers 
consisting  of — 


Axis  cylinder 
and 

'  Medullary  sheath. 

,  Neuroglia  cells. 


Connective  tissue. 


Blood  vessels. 


FIG.  425. — FROM  A  CROSS  SECTION  OF  THE  HUMAN 
SPINAL  CORD  IN  THE  REGION  OF  THE  LATERAL 
FUNICULUS.  X  1 80. 


SPINAL    CORD 


415 


As  the  nerve  fibers  which  occupy  the  interstices  of  the  neuroglia  net- 
work increase  in  number  and  acquire  myelin  sheaths,  thus  becoming  larger, 
the  protoplasm  of  the  neuroglia  is  compressed  into  stellate  accumulations, 
often  surrounding  a  nucleus  (Fig.  428,  A).  In  Golgi  preparations  they 
appear  as  in  Fig.  427,  and  are  described  as  long  rayed,  and  short  rayed 
or  mossy  cells.  These  forms  represent  clumps  of  neuroglia  fibers,  some- 
times clogged  with  precipitate,  in  the  center  of  which  there  may  or  may 
not  be  a  nucleus. 

The  nerve  fibers  of  the  white  substance  vary  in  diameter,  the  coarsest 
being  found  in  the  ventral  funiculi  and  lateral  parts  of  the  dorsal  funiculi; 


c 


FIG.  426. — NEUROGLIA  CELLS  AND  FIBERS  FROM  THE  SPINAL  CORD  OF  AN  ELEPHANT.     (Hardesty.) 
c-i,  Successive  stages  in  the  transformation  of  neuroglia  cells,  ending  with  disintegrating  nuclei; (i) ;  1,  a 
leucocyte.    Benda's  stain.     X  94O. 

the  finest  are  in  the  medial  parts  of  the  dorsal  and  lateral  funiculi.  Else- 
where coarse  and  fine  fibers  are  intermingled.  Their  general  direction 
is  parallel  with  the  long  axis  of  the  cord.  Like  other  nerve  fibers  they 
consist  of  fibrillae  imbedded  in  neuroplasm.  Most  of  them  are  medullated, 
and  in  cross  section  the  myelin  often  forms  concentric  rings.  Although  a 
few  observers  have  described  nodes,  it  is  generally  considered  that  there 
are  no  nodes  in  the  central  nervous  system.  During  the  development  of 
the  myelin,  fibers  have  been  found  encircled  by  sheath  cells,  Fig.  428,  B, 
as  described  by  Hardesty  (Amer.  Journ.  Anat.,  1905,  vol.  4,  p.  329-354). 
In  longitudinal  view,  these  sheath  cells  are  seen  in  depressions  of  the 
myelin,  where  they  greatly  resemble  the  neurolemma  cells  of  peripheral 


416 


HISTOLOGY 


Short  rayed  cells. 


Long  rayed  cells. 


FIG.  427. — NEUROGLIA  CELLS  FROM  THE  BRAIN  OF  AN  ADULT   MAN. 
Golgi  Method.     X  280. 


nerves.  With  the  increase  of  myelin  the  sheaths  become  very  slender  and 
can  seldom  be  detected  in  the  adult.  It  is  ordinarily  stated  that  the  medul- 
lated  fibers  of  the  central  nervous  system  are  without  a  neurolemma. 

Gray  Substance.     The  gray  substance  consists  of  neuroglia,  nerve  cells, 
and  a  confused  mass  of  non-medullated  nerve  fibers  running  in  all  direc- 
tions.      The     nerve 

'dvessds-       -  cells     are    of    three 

types:  (i)  large 
motor  cells  with  pro- 
cesses which  enter  the 
peripheral  nerves;  (2) 
cells  with  processes 
limited  to  the  central 
nervous  system  and 
extending  through  its 
white  substance  from 
one  part  to  another; 
and  (3)  small  cells 
with  processes  con- 
fined to  the  gray  sub- 
stance. The  neurax- 
ons  of  cells  of  the  third  type  branch  freely,  and  they  may  cross  to  the 
gray  substance  on  the  opposite  side  of  the  cord. 

The  motor  cells  occur  in  groups  in  the  ventral  columns  (horns).  In 
the  cervical  and  lumbar  enlargements  there  are  two  groups,  a  ventro- 
medial  and  a  dor  so-lateral  (Fig. 
424),  which  unite  in  the  upper  cer- 
vical and  thoracic  portions  of  the 
cord;  less  well  defined  are  the 
dorso-medial  and  ventro-lateral 
groups.  In  all  of  these  groups 
the  motor  cells  are  large  (67-135  /z 
in  diameter),  with  round  or  oval 
nuclei  and  prominent  nucleoli 
(Figs.  429  and  430).  Their  proto-  A» 
plasm  appears  densely  granular 
in  ordinary  preparations,  but  when 
specially  treated  it  is  seen  to  con- 
tain an  abundance  of  neurofibrils; 

if  preserved  in  alcohol  and  stained  with  methylene  blue,  the  groups  of 
granules  known  as  Nissl's  bodies  may  be  demonstrated.  As  already 
noted,  these  are  abundant  in  vigorous  cells  but  become  reduced  or  dis- 
appear in  various  conditions  of  exhaustion.  Granules  of  brownish 


c  a.c-  _ 

FIG.  428. 

Neuroglia  cells  and  nerve  fibers  from  a  cross 
section  of  the  spinal  cord  of  an  elephant.  B, 
Neuroglia  cells,  nerve  fibers  and  sheath  cells,  from 
the  spinal  cord  of  a  pig,  2  weeks  after  birth.  C, 
Isolated  fiber  from  the  cord  of  21  cm.  pig  embryo, 
stained  with  osmic  acid.  (After  Hardesty.)  a. 
c.,  Axis  cylinder;  my.,  myelin;  n.,  neuroglia 
nuclei;  n.  f.,  neuroglia  fibrils;  s.  c.,  sheath  cell. 


SPINAL   CORD 


417 


pigment  are  sometimes  conspicuous.  All  of  these  features  may  be  ob- 
served in  the  smaller  nerve  cells,  but  they  are  most  evident  in  the  large 
motor  cells.  The  dendrites  of  the  motor  cells  extend  far  into  the  dorsal 
columns  (horns),  and  they  even  pass  out  of  the  gray  substance  into  the 
ventral  and  lateral  funiculi.  The  neuraxon  begins  as  a  slender  non- 
medullated  fiber  at  the  tip  of  a  clear  "implantation  cone"  and  acquires 
its  myelin  sheath  as  it  crosses  the  white  layer.  Ordinarily  it  has  no  colla- 
terals; when  present  they  are  very  small.  None  of  the  neuraxons  cross 
to  the  opposite  side  of  the  cord  before  entering  the  motor  roots. 

The  nerve  cells  of  the  second  type,  usually  smaller  than  the  motor 
cells  but  more  abundant,  are  distributed  throughout  the  gray  substance 
either  singly  or  in  groups.  Definite  groups  of  nerve  cells  in  the  spinal 
cord  and  brain  are  known  as  nuclei,  and  at  the  root  of  the  dorsal  column 
(horn)  near  its  junction  with  the  gray  commissure,  there  is  the  important 


FIG.  429. — NERVE   CELL   OF   THE  SPINAL  CORD       FIG.  430. — NERVE  CELL  OF  THE  SPINAL  CORD  OF 
OF  A  DOG.     X  600.  A  CHILD.     X  430. 

dorsal  nucleus  (column  of  Clarke).  It  is  composed  of  cells  which  send 
their  neuraxons  into  the  lateral  funiculus,  in  which  they  ascend  to  the 
cerebellum.  The  dorsal  nucleus  is  limited  to  the  thoracic  portion  of  the 
cord,  and  adjacent  parts  of  the  lumbar  and  cervical  regions. 

The  fibers  of  the  ground  bundles  are  derived  from  scattered  cells  of 
the  second  type.  Their  dendrites  are  long  but  sparingly  branched. 
The  neuraxons  give  off  collaterals  in  the  gray  substance,  and  enter  the 
ventral  and  lateral  funiculi  (rarely  the  dorsal)  of  the  same  or  opposite 
side.  In  the  white  substance  most  of  them  divide  into  ascending  and 
descending  fibers,  which  send  collaterals  back  into  the  gray,  either  singly 
or  in  bundles,  and  the  main  branches  finally  terminate  like  the  collaterals. 
After  re-entering  the  gray  substance  they  ramify  freely  around  the  motor 
cells. 

In  transverse  sections  the  dorsal  column  appears  capped  by  the  zona 
spongiosa  which  covers  the  substantia  gelatinosa  (Fig.  424).  The  former 
contains  spindle-shaped  "marginal  cells"  which  send  fibers  into  the 
white  substance.  The  substantia  gelatinosa  contains  a  limited  number 
of  very  small  nerve  cells  which  send  processes  into  the  zona  terminalis 
27 


4i8 


HISTOLOGY 


(Fig.  424);  it  contains  also  stellate  neuroglia  cells,  the  processes  of  which 
are  said  to  become  transformed  into  a  granular  substance. 

Ependyma.  The  ependyma  is  that  part  of  the  neuroglia  which  lines 
the  central  canal.  It  appears  like  a  simple  columnar  epithelium,  but  its 
cell-like  bodies  are  the  ends  of  strands  which  primarily  extend  clear 
across  the  spinal  coird  to  the  external  limiting  membrane.  A  nucleus  is 
generally  found  in  the  strand  near  the  central  canal,  and  there  may  be 
others  further  out  (Fig.  431).  Although  in  the  embryo  strands  may 
readily  be  traced  from  the  central  canal  to  the  periphery,  in  the  adult 
they  are  generally  broken  up  into  stellate  cells,  or  forms  retaining  a  chief 

From  the  substantia  gelatinosa  of  a  newborn  rat. 

Neuroglia  cell. 


Central  canal.  ~ 


Ependymal  cells. ' 


Neuroglia  ,cell    of  the 

white   substance  from 

a  cat  6  weeks  old. 


•  Chief  process. 


Neuroglia  cell  of  the  gray  substance  of  the  base 

».«.  ,.  ~~~~  ~~.  of  the  dorsal  column  of  a  human  embryo. 

FIG.  431. — NEUROGLIA  CELLS  FROM  THE  SPINAL  CORD.     X  280. 


Concentric  neuroglia  cell  from  a  cat 
six  weeks  old. 


process  directed  either  toward  the  central  canal  or  the  periphery  (Fig.  431). 
All  these  cells  are  parts  of  a  general  syncytium,  as  already  described. 

The  ependymal  cells  at  birth,  and  for  sometime  afterwards,  possess 
cilia  projecting  into  the  central  canal,  but  in  the  adult  these  disappear. 
It  is  questionable  whether  or  not  they  are  motile.  Single  bodies  have 
been  found  at  their  bases,  but  not  diplosomes. 

Surrounding  the  central  canal,  outside  of  the  ependymal  layer,  there 
is  a  zone  of  central  gray  substance,  characterized  by  concentrically  ar- 
ranged neuroglia  cells,  one  of  which  is  shown  in  Fig.  431. 

BRAIN. 

Development  and  General  Features.  If  a  human  embryo  of  4  mm.  is 
placed  in  such  a  position  that  the  spinal  portion  of  the  medullary  tube  is 


BRAIN 


419 


approximately  vertical,  the  anterior  end  of  the  tube,  from  which  the 
brain  develops,  is  bent  as  shown  in  Fig.  432,  A.  The  first  portion,  begin- 
ning at  the  anterior  extremity  where  the  neuropore  is  still  open,  passes 
vertically  upward.  At  the  head-bend  it  turns  backward  and  passes  to  the 
neck-bend,  where  it  curves  downward,  becoming  continuous  with  the 
part  of  the  tube  which  forms  the  spinal  cord.  The  anterior  ascending 
portion  is  the  fore-brain  (prosencephalon) ;  the  part  where  the  head-bend 
occurs  is  the  mid-brain  (mesencephalon) ;  and  the  remainder  is  the  hind- 
brain  (rhomb  encephalon) .  These  three  fundamental  parts  have  become 
more  distinct  and  exhibit 
subdivisions  in  the  10  mm. 
embryo  shown  in  Fig.  432,  B. 

Prosencephalon.  The 
fore-brain  becomes  subdi- 
vided into  the  telencephalon 
anteriorly,  and  the  dienceph- 
alon  posteriorly;  the  latter 
connects  with  the  mid-brain. 
In  very  early  stages  the  fore- 
brain  produces  two  lateral 
outpocketings,  one  on  either 
side,  called  the  optic  vesicles. 
Each  expands  distally  to 
form  the  retina  of  an  eye, 
and  its  connection  with  the 
fore-brain  becomes  reduced 
to  a  slender  stalk.  In  later 
stages,  the  depression  on  the 
inner  wall  of  the  brain  which 
marks  the  position  of  the 
stalk  is  called  the  optic  re- 
cess. It  is  shown  in  the  me- 
dian sagittal  sections  of  the  brain  of  an  embryo  of  three  months  and  of 
an  adult,  in  Figs.  433  and  434  respectively. 

Telencephalon.  The  principal  derivatives  of  the  telencephalon  are  a 
pair  of  lateral  outpocketings  which  arise  somewhat  later  than  the  optic 
vesicles  and  are  known  as  the  cerebral  hemispheres.  Each  contains  a 
cavity,  or  lateral  ventricle,  which  opens  into  the  medullary  tube  through 
the  interventricular  foramen  (foramen  of  Monro).  In  later  stages  this 
foramen  is  relatively  small,  and  it  appears  in  Figs.  433  and  434  as  a  darkly 
shaded  cleft  in  front  of  the  thalamus  (th.).  As  the  hemispheres  expand, 
they  approach  one  another  in  the  median  line  above  the  brain,  being  sep- 
arated by  a  thin  plate  of  connective  tissue.  They  grow  backward,  cover- 


sp.c. 


FIG.  432. — A,  THE  BRAIN  OF  A  4.0  MM  HUMAN  EMBRYO 
(after  Bremer);  B,  THE  BRAIN  OF  A  10.2  MM.  EMBRYO 
(after  His). 

Except  the  isthmus,  is.  the  principal  subdivisions  of  the  brain 
are  indicated  by  prefixes  of  the  term  encephalon;  sp.  c., 
spinal  cord;  h.,  hemisphere;  o.  v.,  optic  vesicle;  r.,  rhinen- 
cephalon;  v.,  roof  of  the  fourth  ventricle. 


420 


HISTOLOGY 


ing  all  the  hind  part  of  the  brain.     Their  outer  walls  (constituting  the 
pallium,  or  mantle)  become  convoluted,  forming  gyri,  with  intervening 


FIG.  433. — SAGITTAL  SECTION  OF  THE  BRAIN  OF  AN  EMBRYO  OF  THREE  MONTHS.     (After  His.) 
cbl.,  Cerebellum;  hem.,  hemisphere;  hy.,  hypophysis  (posterior  lobe) ;  isth.,  isthmus;  med.,  medulla  oblon- 
gata;  mes.,  mesencephalon;  ol.  b.,  olfactory  bulb;  o.  r.,  optic  recess;  p.,  pons;  p.  b.,  pineal  body;  p  s. 
pars  subthalamica;  th.,  thalamus. 


, 
O.b. 


cbl. 


FIG.  434. — MEDIAN  SAGITTAL  SECTION  OF  AN  ADULT  BRAIN. 

cbl.,  Cerebellum:  c.  c.,  corpus  callosum;  c.  q.,  corpora  quadrigemina ;  f.,  body  of  the  fornix;  hy.,  posterior 
lobe  of  the  hypophysis;  med.,  medulla  oblongata;  o.  b.,  olfactory  bulb;  o.  r.,  optic  recess;  p.,  pons; 
p.  D.,  pineal  body;  p.  s.,  pars  subthalamica;  s.  p.,  septum  pellucidum;  th.,  thalamus. 

sulci,  and  each  hemisphere  as  a  whole  is  divided  into  frontal,  parietal, 
occipital  and  temporal  lobes,  as  described  in  works  on  gross  anatomy.     A 


BRAIN  421 

more  independent  subdivision  of  the  hemisphere  is  the  olfactory  lobe, 
which  terminates  anteriorly  in  the  olfactory  bulb — an  expansion  which 
receives  the  olfactory  nerves.  The  entire  olfactory  portion  of  the  brain 
is  called  the  rhinencephalon. 

Connecting  the  hemispheres  with  one  another,  there  is  a  great  transverse 
commissure  known  as  the  corpus  callosum  (Fig.  434,  c.c.).  Below  this  is 
the  arched  body  ofthefornix  (f),  representing  a  median  fusion  of  two  longi- 
tudinal bundles  of  commissural  fibers,  only  small  parts  of  which  are  in- 
cluded in  a  median  section.  Between  the  corpus  callosum  and  the  for- 
nix,  there  is  a  thin  septum  pellucidum  which  consists  of  two  vertical  plates 
with  a  closed  cleft-like  cavity  between  them. 

It  is  probable  that  the  corpus  callosum  and  body  of  the  fornix  develop  in  a  thicken- 
ing of  the  front  wall  of  the  telencephalon,  where  it  crosses  the  median  line.  The  cavity 
of  the  septum  pellucidum  is,  accordingly,  a  secondary  cleft  in  the  thickened  wall. 
A  fusion  between  the  adjacent  medial  walls  of  the  hemispheres,  to  provide  a  path  for 
the  fibers  of  the  corpus  callosum  and  to  account  for  the  cavity  in  the  septum,  has  been 
described,  but  not  confirmed. 

In  addition  to  the  hemispheres  with  their  commissures  and  olfactory 
lobes,  and  the  optic  vesicles  which  are  not  counted  as  a  part  of  the  brain, 
the  telencephalon  produces  the  pars  optica  hypothalami.  This  "optic 
portion  of  the  region  below  the  thalamus"  includes  the  optic  recess,  and 
in  the  mid-ventral  line  it  forms  a  funnel-shaped  depression,  the  infun- 
dibulum,  terminating  below  in  the  posterior  lobe  of  the  hypophysis.  (The 
anterior  lobe  of  the  hypophysis  is  derived  from  the  pharynx.)  The 
median  cavity  of  the  telencephalon  is  a  laterally  compressed  space  which 
forms  the  front  part  of  the  third  ventricle.  The  lateral  ventricles,  which 
open  from  it,  are  counted  as  the  first  two. 

Diencephalon.  In  the  mid-dorsal  line  the  diencephalon  produces  a 
cone-like  body,  the  corpus  pineale.  Laterally,  in  its  thick  walls,  there 
is  a  mass  of  gray  substance  called  the  thalamus  (bed).  External  to  the 
thalamus  are  the  great  bundles  of  fibers  passing  from  the  hemispheres 
to  the  spinal  cord.  The  sensory  fibers  ascending  from  the  cord  terminate 
in  the  thalami,  where  there  is  a  relay  of  nerve  cells  to  convey  the  impulses 
to  the  hemispheres.  The  thalami  have  other  connections  of  equal  impor- 
tance. They  come  in  contact  with  one  another  across  the  cleft-like  cavity 
of  the  diencephalon  (which  is  a  part  of  the  third  ventricle)  and  may  fuse, 
forming  the  massa  intermedia.  The  ventricle  surrounds  this  mass.  Be- 
neath the  thalamus  the  diencephalon  forms  the  pars  mammillaria  hypo- 
thalami, which  is  represented  on  the  under  surface  of  the  brain  by  the  pair 
of  rounded  mammillary  bodies,  one  on  either  side  of  the  median  line 
(Fig.  435,  B). 

Mesencephalon.  The  mid-brain  remains  undivided,  and  its  walls 
become  very  thick.  Dorsally  it  forms  four  rounded  elevations,  the 


422 


HISTOLOGY 


corpora  quadrigemina  (Fig.  435,  A).  These  are  arranged  in  pairs,  the 
anterior  pair  being  known  as  the  superior  colliculi,  and  the  posterior  as 
the  inferior  colliculi;  the  former  have  important  relations  with  the  optic 
tracts,  and  the  latter  with  the  auditory  tracts.  On  the  under  side  of  the 
mid-brain  there  are  two  great  bundles  of  fibers,  the  cerebral  peduncles 
(pedunculi  cerebri),  which  diverge  as  they  pass  forward  from  the  hind-brain, 
and  swing  upward  on  the  sides  of  the  mid-brain  to  connect  with  the  hemi- 
spheres (Fig.  435).  Between  the  cerebral  peduncles  on  the  under  side  of 
the  mid-brain,  the  oculomotor  nerves  emerge.  They  are  derived  from 
groups  of  motor  cells  situated  just  beneath  the  floor  of  the  cavity  of  the 
mid-brain.  This  cavity  remains  a  slender  tube  and  is  known  as  the 
cerebral  aqueduct  (aquaductus  cerebri). 


£:;£V££SX-  oc. 


A  B 

FIG.  435. — A,  DORSAL  AND  B,  VENTRAL   VIEW  OF  THE   POSTERIOR  PART   OF   THE  ADULT   BRAIN.     THE 

CEREBELLUM  AND  ROOF  OF  THE  FOURTH  VENTRICLE  HAVE  BEEN  REMOVED  FROM  A. 

b.  c.,  Brachium  conjunct! vum ;  b.  p.,  brachium  pontis;  c.  m.,  corpus  mamillare;  c.  p.,  cerebral  peduncle; 
c.  q.  a.,  and  c.  q.  p.,  anterior  and  posterior  corpora  quadrigemina;  inf.,  inf undibulum ;  med.,  medulla; 
ol.,  olive;  p.,  pons;  p.  b.,  pineal  body;  pyr.,  pyramid;  r.  b.,  restiform  body;  ven.,  floor  of  fourth  ventri- 
cle. _  The  nerves  are — oc.,  oculomotor;  tr.,  troclear;  tri.,  trigeminal;  abd.,  abducens;  int.,  intermedius, 
fa.,  its  facial  portion;  ac.,  acoustic;  glo.,  glossopharyngeal;  va.,  vagus,  ace.,  its  accessory  portion; 
ny.,  hypoglossal. 


Between  the  mid-brain  and  the  hind-brain  there  is  a  marked  constric- 
tion, known  as  the  isthmus  (Fig.  432,  B).  From  the  dorsal  surface  of  the 
isthmus  the  trochlear  nerves  make  their  exit  (Fig.  435,  A);  they  are 
processes  of  nerve  cells  situated  beneath  the  floor  of  the  cavity,  but  they 
pass  to  the  dorsal  surface  and  cross  to  the  opposite  side  before  emerging. 

Rhombencephalon.  The  rhombencephalon  (or  hind-brain)  receives  its 
name  from  the  diamond  shape  which  it  presents  when  seen  from  above. 
This  form  is  established  in  young  embryos  and  persists  in  the  adult  (Fig. 
435>  A).  The  roof  of  the  rhombic  cavity  becomes  a  thin  membrane  and 
is  readily  torn  away,  but  the  sides  and  especially  the  floor  are  greatly 
thickened.  The  form  of  the  hind-brain  may  be  imitated,  as  described 
by  His,  by  cutting  a  short  slit  in  the  upper  side  of  a  piece  of  rubber  tubing 


BRAIN 


423 


and  forcing  the  ends  toward  one  another;  the  region  with  the  weakened 
dorsal  wall  buckles  downward  and  bulges  toward  either  side.  The  most 
prominent  part  of  the  embryonic  hind-brain,  as  it  buckles  downward,  be- 
comes the  pons  in  the  adult.  From  the  dorsal  part  of  the  front  end  of 
the  hind-brain,  the  cerebellum  develops,  overhanging  the  thin  roof  of  the 
posterior  portion.  Pons  and  cerebellum  are  thus  both  derived  from  the 
anterior  part  of  the  rhombencephalon,  which  is  set  apart  as  the  meten- 
cephalon;  the  remainder  of  the  hind-brain  is  included  in  the  myelencephalon 
(Fig.  432),  which  becomes  the  medulla  oblongata  and  is  continuous  with 
the  spinal  cord. 

Before  considering  the  subdivisions  of  the  hind-brain  in  further  detail, 
the  relation  of  the  principal  parts  of  the  adult  brain  to  the  primary 
vesicles  may  be  reviewed  in  the  following  table: 


Fore-brain 


Telencephalon. . . 


Mid-brain. 


Hind-brain 


(  Diencephalon .... 


{  Mesencephalon  . . . 


Hemisphere : 

Pallium. 

Rhinencephalon. 

Corpus  callosum. 
Optic  part  of  the  hypothalamus. 

Hypophysis   (posterior  lobe). 

Pineal  body. 
Thalamus. 

Mammillary  part  of  the  hypothal- 
amus. 

Corpora  quadrigemina. 
Cerebral  peduncles. 


( Isthmus Isthmus. 

Metencephalon...(Cerebellum- 
1  Pons. 

Myelencephalon. .     Medulla  oblongata. 


Metencephalon.  The  pons,  as  seen  from  the  under  side  of  the  brain 
(Fig.  435,  B),  appears  as  a  broad  bundle  of  transverse  fibers  interrupted 
for  the  passage  of  the  motor  and  sensory  roots  of  the  trigeminal  nerve. 
The  superficial  fibers  of  the  pons  pass  dorsally  around  the  wall  of  the 
brain-tube,  forming  a  pair  of  arms,  the  brachia  pontis,  which  enter  the 
cerebellum.  In  addition  to  these  large  bundles,  the  cerebellum  receives 
fibers  through  the  brachia  conjunctiva  which  extend  into  it  from  the 
isthmus,  and  also  from  the  restiform  bodies  (i.e.,  rope-like)  which  ascend 
from  the  posterior  part  of  the  hind-brain  (Fig.  435,  A).  Thus  on  either 


424 


HISTOLOGY 


side  the  cerebellum  connects  with  three  bundles  of  fibers,  which  come 
together  to  form  its  medulla  (corpus  medullare).  The  medulla  is  sur- 
rounded by  the  gray  cortical  substance,  and  the  entire  cerebellum  is 
divided  into  many  lobes  and  lobules. 

The  cavity  of  the  hind-brain,  which  is  continous  posteriorly  with  the 
central  canal  of  the  cord,  and  anteriorly  with  the  cerebral  aqueduct, 
is  known  as  the  fourth  ventricle.  It  extends  upward  toward  the  medulla 
of  the  cerebellum,  forming  a  tent-like  recess,  the  apex  of  which  is  the 
fastigium. 

Myelencephalon.  The  my elencephalon  becomes  the  medulla  oblon- 
gata,  continuous  without  demarcation  with  the  medulla  spinalis  or  spinal 
cord.  The  ventral  median  fissure  becomes  shallow,  but  it  may  be  traced 
to  the  pons  (Fig.  435,  B).  On  either  side  of  its  upper  portion,  there  is  an 
elongated  swelling,  the  pyramid,  corresponding  in  position  with  the 
ventral  funiculus  of  the  cord.  Each  pyramid  is  bounded  laterally  by 
the  ventro-lateral  groove,  from  which  the  motor  roots  of  the  hypoglossal 
nerve  emerge;  this  groove  is  continuous  with  the  ventro-lateral  groove  of 
the  cord,  from  which  the  motor  roots  of  the  spinal  nerves  proceed.  Near 
the  pons  the  abducent  nerve  comes  out  close  beside  this  groove.  The 
dorso-lateral  groove  of  the  cord  likewise  extends  to  the  pons;  and  in  line 
with  the  dorsal  roots  of  the  cord;  the  sensory  roots  of  the  vagus,  glosso- 
pharyngeal,  acoustic  and  facial  nerves  enter  this  groove.  The  lateral 
roots  of  the  accessory,  glossopharyngeal  and  facial  nerves  emerge  just 
below  them.  The  space  between  the  ventro-lateral  and  dorso-lateral 
grooves  corresponds  with  the  lateral  funiculus  of  the  cord.  Toward  the 
upper  end  of  the  medulla,  it  presents  a  rounded  swelling  known  as  the 
olive. (Fig.  435>  B)- 

The  dorsal  funiculus  of  the  upper  part  of  the  cord  is  divided  into  the 
medial  gracile  and  lateral  cuneate  fasciculi;  these  may  be  followed  into 
the  medulla  where  they  become  broader  (Fig.  435,  A).  Some  of  their 
fibers  enter  the  restiform  body,  and  pass  to  the  cerebellum;  others  pass 
downward  on  either  side  of  the  central  canal  and  continue  beneath  the 
floor  of  the  fourth  ventricle  to  the  hemispheres.  Where  the  central  canal 
expands  to  become  the  thin-roofed  fourth  ventricle,  all  nerve  fibers  either 
pass  downward  into  its  floor,  or  turn  aside  to  enter  the  restiform  body. 

MEDULLA   OBLONG  AT  A. 

The  study  of  the  medulla 'oblongata  requires  full  consideration  of  the 
fiber  tracts  of  the  cord  and  anterior  portion  of  the  brain,  which  cannot  here 
be  taken  up;  only  a  few  of  the  most  fundamental  features  of  the  medulla 
are  to  be  mentioned.  Sections  through  the  lower  end  of  the  medulla  re- 
semble those  of  the  cord,  and  the  gray  substance  retains  the  form  of 


MEDULLA    OBLONGATA 


425 


an  H.  The  fibers  from  the  hemispheres,  which  descend  to  the  motor 
cells  of  the  cord,  run  mostly  in  the  lateral  funiculi,  as  previously  stated. 
They  descend  from  the  brain,  however,  in  the  ventral  funiculi,  in  which 
they  form  the  pyramids  in  the  upper  part  of  the  medulla  (Fig.  437). 
In  the  lower  part  of  the  medulla  they  decussate,  crossing  to  the  lateral 
funiculus  of  the  opposite  side,  as  shown  in  Fig.  436;  they  appear  to  cut 
off  the  ventral  columns  (horns)  from  the  remainder  of  the  gray  H. 
Then  they  descend  in  the  spinal  cord  as  the  lateral  cerebro- spinal  tract 
(also  called  crossed  pyramidal).  A  few  fibers,  however,  descend^ini  the 
ventral  funiculi  of  the  cord  without  having  crossed  in  the  medulla.  Such 
fibers  of.  the  ventral  cerebro- spinal  tract  (direct  pyramidal)  cross  to  the  op- 


t.s.n.l. 


f.c.l: 


n.  ace: 


f.c.v. 


FIG.  436. — SECTION  AT  THE  LEVEL  OF  THE 
FIRST  CERVICAL  NERVE.  (After  Dejerine.) 

The  right  half  of  the  section  shows  the  effect 
of  Weigert's  stain,  the  myelinated  portions 
being  dark;  the  left  half  shows  the  gray 
substance  stippled;  the  white  is  blank,  f. 
c.,  Fasciculus  cuneatus;  f.  c.  1.,  fasciculus 
cerebro-spinalis  lateralis;  f.c.v.,  fasciculus 
cerebro-spinalis  ventralis;  f.  g.,  fasciculus 
gracilis;  d.  c.,  dorsal  column;  d.  p.,  decus- 
sation  of  the  pyramids;  d.  r.,  dorsal  root  of 
first  cervical  nerve;  v.  c.,  ventral  column. 


d.l 


(After 


FIG.  437. — SECTION  OF  THE  MEDULLA. 
Dejerine.) 

d.  c.,  Dorsal  column;  d.  1.,  decussation  of  the 
lemnisci;  f.  c.,  fasciculus  cuneatus;  n.  ace., 
nucleus  of  the  accessory  nerve ;  n.  c.,  cuneate 
nucleus;  n.  g.,  gracile  nucleus;  py.,  pyramid; 
t.  s.  n.  t.,  spinal  tract  of  the  trigeminal 
nerve;  v.  c.,  ventral  column. 


posite  side  in  the  cord  before  terminating  in  contact  with  the  motor  cells 
of  the  ventral  columns. 

The  fibers  in  the  cerebro-spinal  tracts  are  the  neuraxons  of  the  py- 
ramidal cells  in  the  outer  layers  of  the  hemispheres,  which  will  be  described 
in  a  following  section.  They  descend  through  the  internal  capsule  (which 
in  a  layer  of  white  substance  lateral  to  the  thalami),  thence  through  the 
cerebral  peduncles,  pons,  medulla  oblongata  and  spinal  cord,  without  in- 
terruption. This  motor  path  from  the  hemispheres  to  the  voluntary 
muscles  includes,  therefore,  only  two  neurones  or  nerve  cells,  one  from  the 
cortex  to  the  motor  cells  of  the  ventral  column  of  the  cord,  and  the  other 
from  the  ventral  column  to  the  end  plate  on  the  muscle  fiber.  Other 
motor  fibers  from  the  hemispheres  to  the  cord  terminate  in  the  red  nucleus 
deep  within  the  substance  of  the  mid-brain;  cells  of  the  red  nucleus  send 
neuraxons  to  the  opposite  side,. and  these  descend  in  the  lateral  funiculi 
of  the  cord  as  the  rubro-spinal  tract.  They  terminate  in  relation  with 


426 


HISTOLOGY 


t.s.  n.h. 


motor  cells  on  the  same  side,  and  thus  is  formed  a  motor  path  composed 
of  three  neurones.  Other  tracts  to  the  cord  proceed  from  the  cerebellum. 
The  motor  nerves  of  the  medulla  oblongata,  pons,  and  mid-brain  arise 
from  groups  of  cells,  or  nuclei,  which  are  typically  near  the  median  line  and 
only  a  short  distance  below  the  floor  of  the  ventricle  or  cavity.  Fig.  438 
includes  the  nucleus  of  the  hypoglossal  nerve,  which  is  in  this  position. 
The  lateral  motor  roots  are  further  below  the  ventricle  and  are  more  lat- 
eral. The  nucleus  ambiguus,  which  is  an  elongated  structure  containing 
the  motor  cells  of  the  accessory,  vagus  and  glossopharyngeal  nerves,  is  of 

this  sort  (Fig.  438).  These 
motor  nuclei  correspond  with 
cell  groups  in  the  ventral 
columns  of  the  cord,  and 
they  are  similarly  in  connec- 
tion with  fibers  from  the 
pyramidal  cells  of  the  hemis- 
pheres. In  so  far  as  the 
latter  pass  to  these  cerebral 
nerves,  they  form  the  cortico- 
bulbar  tract,  "bulb"  being  a 
general  term  for  the  ex- 
panded part  of  the  hind- 
brain.  The  cortico-bulbar 
fibers  decussate  at  different 
levels. 

Somewhat  higher  in  the 
medulla  than  the  decussation 

of  the  descending  motor  fibers  or  pyramids,  the  sensory  fibers  ascending  in 
the  gracile  and  cuneate  fasciculi  terminate  in  relation  with  groups  of  cells 
known  as  the  gracile  and  cuneate  nuclei  respectively  (Fig.  437).  They  ap- 
pear as  additional  horns  of  gray  substance.  The  neuraxons  from  the  cells 
in  these  nuclei  pass  ventrally  and  decussate  beneath  the  central  canal,  as 
shown  in  Fig.  437.  The  bundles  to  which  they  give  rise  are  known  as  the 
medial  lemnisci  or  fillets.  In  their  course  through  the  upper  part  of  the 
medulla,  they  are  vertically  placed  bands  of  longitudinal  fibers,  on  either  side 
of  the  median  line  (Fig.  438).  The  fillets  not  only  receive  fibers  of  muscle 
sense  through  the  gracile  and  cuneate  fasciculi,  but  they  are  joined  by  the 
spino-thalamic  fasciculi  of  fibers  of  cutaneous  sense,  which  pass  up  the 
cord  in  the  lateral  funiculi.  Moreover,  they  receive  accessions  from  the 
cerebral  sensory  nerves.  The  fibers  of  the  latter  enter  the  medulla  and 
divide  into  ascending  and  descending  branches,  like  the  dorsal  root  fibers 
of  the  spinal  nerves,  but  the  descending  fibers  are  relatively  longer.  The 
position  of  the  descending  fibers  of  the  trigeminal  nerve  (tractus  spinalis 


FIG.  438. — SECTION  OF  THE   MEDULLA.     (After   Dejerine.) 

c.  r.,  Corpus  restiforme;  f.  c.  o.,  cerebello-oliyary  fibers;  lem., 
lemniscus  or  fillet;  n.  am.,  nucleus  ambiguus;  n.  h.,  nu- 
cleus hypoglossi;  ol.,  olive;  py.,  pyramid;  t.  s.,  tractus 
solitarius;  t.  s.  n.  t.,  tractus  spinalis  nervi  trigemini;  v., 
fourth  ventricle. 


MEDULLA    OBLONGATA  427 

nervi  trigemini)  is  shown  in  Fig.  438,  and  the  tractus  solitarius,  containing 
sensory  fibers  from  the  vagus  and  glossopharyngeus,  is  shown  in  the  same 
figure.  In  connection  with  these  bundles  of  sensory  fibers,  there  are 
groups  of  nerve  cells  forming  the  nucleus  of  the  tractus  solitarius,  and 
nucleus  of  the  spinal  tract  of  the  trigeminal  nerve.  These  correspond  with 
the  gracile  and  cuneate  nuclei,  and  send  fibers  into  the  fillets.  The  fillets 
continue  through  the  pons  and  cerebral  peduncles  to  the  thalami,  in 
which  they  terminate.  Nerve  cells  of  the  thalami  convey  the  impulses 
received  onward  to  the  hemispheres.  Thus  the  sensory  tract  is  com- 
posed of  three  neurones,  the  first  being  in  the  ganglia  of  the  sensory 
nerves,  outside  of  the  central  nervous  system;  the  second  begins  in  the 
gracile  and  cuneate  nuclei,  or  in  the  gray  substance  of  the  cord  in  case 
the  impulse  travels  by  the  spino-thalamic  tract,  or  in  the  nuclei  asso- 
ciated with  central  tracts  of  the  sensory  cerebral  nerves,  and  in  all  three 
cases  extends  to  the  thalamus;  the  third  begins  in  the  thalamus  and 
extends  to  the  cerebral  cortex. 

CEREBELLUM. 

The  medullated  nerve  fibers  of  the  restiform  bodies,  brachia  pontis, 
and  brachia  conjunctiva  come  together  to  form  the  medulla  of  the  cere- 
bellum, and  place  the  cerebellum  in  connection  with  spinal  and  cerebral 
nerves  and  with  the  hemispheres.  The  medulla  contains  several  paired 
nuclei,  the  largest  being  the  dentate  nuclei,  which  have  convoluted  gray 
capsules  resembling  those  of  the  olivary  nuclei  (shown  in  Fig.  438). 

The  restiform  bodies  include  the  fibers  derived  from  the  dorsal  nuclei  or  columns 
of  Clarke  in  the  spinal  cord;  these  fibers  ascend  in  the  lateral  funiculi,  within  which  they 
form  the  dorsal  spino-cerebellar  tract  (of  Flechsig).  The  restiform  bodies  contain  also 
fibers  from  certain  cells  in  the  gracile  and  cuneate  nuclei,  and  many  fibers  from  the 
olivary  nuclei,  mostly  of  the  opposite  side.  The  brachia  pontis  contain  fibers  passing 
to  the  cerebellum  from  the  numerous  nuclei  pontis.  The  latter  are  in  connection  with 
fibers  descending  from  the  hemispheres,  thus  forming  cerebro-  or  cortico-cerebellar 
tracts.  Some  fibers  pass  in  the  reverse  direction.  The  brachia  conjunctiva  contain 
fibers  of  the  ventral  spino-cerebellar  tracts  (of  Cowers),  which  arise  from  central  or 
lateral  cells  in  the  gray  substance  of  the  cord,  and  pass  through  the  lateral  funiculi  to 
the  brachia  conjunctiva,  through  which  they  turn  back  to  enter  the  cerebellum.  The 
main  part  of  the  brachia  conjunctiva  consists,  however,  of  fibers  passing  outward 
from  the  cerebellum  and  its  dentate  nucleus,  to  end,  after  decussating,  inthe  red  nuclei 
of  the  mid-brain.  Thence  fibers  pass  on  to  the  thalami  and  hemispheres,  and  also 
downward  to  the  medulla  and  spinal  cord. 

The  medulla  of  the  cerebellum  extends  into  the  small  peripheral  lobules, 
where  it  is  covered  by  the  cortical  substance  (Fig.  439).  The  latter 
consists  of  three  strata — an  inner  granular  stratum,  which  is  rust-colored 
in  the  fresh  condition;  a  middle  ganglionic  stratum,  composed  of  a  single 
row  of  large  cell  bodies;  and  an  outer  gray  stratum. 


428 


HISTOLOGY 


Gray  stratum. 


—  Ganglionic  stratum. 


The  inner  granular  stratum  consists  of  many  layers  of  small  cells  which 

by  ordinary  methods  show 
relatively  large  nuclei  and 
very  little  protoplasm.  With 
the  Golgi  method  it  appears 
that  besides  neuroglia  cells, 
two  sorts  of  nerve  cells  are 
present,  the  small  and  large 
granule  cells;  the  former  (Fig. 
440)  are  multipolar  ganglion 
cells  with  short  dendrites 
having  claw-like  termina- 
tions, and  slender  non- 
medullated  neuraxons  which 
ascend  perpendicularly  to  the 
gray  layer  and  there  divide 
in  T-form  into  two  branches. 
The  branches  run  lengthwise 
of  the  transverse  folds  or 
convolutions  of  the  cere- 
bellum and  have  free  un- 
branched  endings.  In  sagit- 
tal sections  (Fig.  442)  the 
terminal  branches  of  the  neuraxons  are  cut  across.  The  small  granule 
cells  form  the  bulk  of  the  granular  stratum.  The  less  frequent  large 
granule  cells  (Fig.  442)  are 
more  than  twice  the  size  of  the 
small  ones;  their  branched  den- 
drites penetrate  the  gray  stra- 
tum and  their  neuraxons,  going 
in  the  opposite  direction,  are 
soon  resolved  into  very  numer- 
ous branches  which  ramify 
throughout  the  granular  stra- 
tum. 

The  granular  layer  contains 
also  a  thick  network  of  medul- 
lated  fibers  which  enter  it 
chiefly  from  the  white  sub- 
stance. A  part  of  these  fibers 
end  in  the  "eosin  bodies"  of 
the  granular  stratum,  which 


FIG.  439. — FROM  A  SAGITTAL  SECTION  OF  THE  CEREBELLUM 
OF  AN  ADULT  MAN.     X   12. 


FIG.  440. — DIAGRAM  OF  A  SECTION  OF  THE  CEREBELLUM 
LENGTHWISE  OF  THE  TRANSVERSE  CONVOLUTIONS. 
GOLGI'S  METHOD.  (Koelliker.) 

gr.,  Cells  of  the  granular  stratum;  n.  their  neuraxons  in 


the  granular  layer  and  n'.,  in  the  gray  stratum; 
Purkinje's  cells.     (From  Bailey's  "Histology.   ) 

are  heaps  of  stainable  particles  found  between  the  small  cells  (Fig.  441). 


CEREBELLUM 


429 


Eosin  bodies. 


Some  of  the  fibers  form  bundles  parallel  with  the  surface,  running  be- 
tween the  granular  and  ganglionic  strata  in  the  sagittal  direction;  they 
send  branches  into  the  gray  layer.  A  small  portion  of  the  granular  stra- 
tum is  formed  by  the  medullated  neuraxons  of  the  cells  in  the  ganglion 
layer. 

The  middle  ganglionic  stratum  consists  entirely  of  a  single  layer  of 
very  large  multipolar  ganglion  cells,  called  Purkinje's  cells.  Their  oval 
or  pear-shaped  bodies  send  two  large  dendrites  into  the  gray  stratum, 
where  they  form  an  extraordinary  arborization  (Fig.  442)  Their  many 
branches  do  not  extend  in  all  directions  but  are  confined  to  the  sagittal 
plane,  that  is,  to  a  plane  at  right  angles  with  the  long  axes  of  the  convolu- 
tions. When  the  convolutions  are  cut  lengthwise,  Purkinje's  cells  appear 
as  in  Fig.  440.  The  neuraxons  arise 
from  the  deep  surface  of  the  cell  bodies, 
and  as  medullated  fibers  they  pass 
through  the  granular  stratum  to  the 
white  substance.  Within  the  granular 
layer  they  produce  collateral  fibers 
which  branch  and  in  part  run  back  into 
the  ganglionic  layer,  ending  near  the 
bodies  of  other  Purkinje's  cells  (Fig. 
442). 

The  outer  gray  stratum,  of  gray 
color,  contains  two  sorts  of  nerve  cells, 
the  large  and  the  small  cortical  cells. 
The  large  cortical  or  basket  cells  are 

multipolar  ganglion  cells,  the  dendrites  of  which  pass  chiefly  toward  the 
surface.  Their  long  neuraxons,  thin  at  first  but  later  becoming  thicker, 
run  parallel  with  the  surface  in  the  sagittal  plane.  They  send  occasional 
collaterals  toward  the  surface,  and  at  intervals  produce  fine  branches  which 
descend  and  terminate  in  baskets  around  the  bodies  of  Purkinje's  cells 
(Fig.  442),  often  surrounding  also  the  beginning  of  their  neuraxons. 

The  small  cortical  cells,  distinguishable  from  the  basket  cells  since 
their  neuraxons  are  not  in  relation  with  Purkinje's  cells,  may  be  divided 
into  two  types,  connected  by  intermediate  forms.  The  cell  bodies  of  the 
first  type  are  nearly  or  quite  as  large  as  those  of  the  basket  cells.  Their 
two  to  five  dendrites  lie  in  the  sagittal  plane  like  those  of  Purkinje's  cells; 
the  slender  neuraxons,  i  mm.  long  or  more,  sometimes  form  loops  and 
are  characterized  by  abundant  branches  in  their  proximal  parts.  The 
terminal  branches  are  few.  Cells  of  the  second  type  are  in  general  some- 
what smaller;  their  shorter  neuraxons  branch  in  the  immediate  vicinity 
of  the  cell  bodies.  The  elements  of  the  first  type  form  the  bulk  of  the 
relatively  numerous  small  cortical  cells,  and  are  found  throughout  the 


•f?%W4?S3ai£J5 

»*\    IP 


43° 


HISTOLOGY 


gray  stratum,  though  they  are  more  abundant  in  its  superficial  part. 
The  second  type  likewise  appears  throughout  the  gray  stratum. 

The  medullated  nerve  fibers  found  in  the  gray  layer  are  prolonga- 
tions of  those  in  the  granular  stratum.  In  part  they  proceed  toward  the 
surface,  where,  after  losing  their  myelin,  they  end  in  branches  among  the 


Purkinje's  cell. 
Neuraxon  of  a  basket  cell. 


Short-rayed  cell. 
Neuroglia  cell. 


Small  cells  of  the 
cortex     • 

ft 


Collaterals  of  a  Pur- 
kin  je  cell. 


-  Long-rayed 

cell. 


Neuraxon   of  a  large 
cell  of  the  granular 

stratum. 
Fibers  to  the  cortex. 

Small  cells  of  the  gran- 
ular stratum. 

FIG.  442. — DIAGRAM  OF  A  SAGITTAL  SECTION  OF  THE  CEREBELLUM. 

Except  the  large  granule  cell,  which  is  from  a  kitten,  the  cells  are  drawn  from  Golgi  preparations  from  an 
adult  man.     K,  large  cortical  or  basket  cell. 

dendrites  of  Purkinje's  cells;  in  part  they  run  between  the  bodies  of 
Purkinje's  cells  lengthwise  of  the  convolutions. 

The  neuroglia  of  the  cerebellum  consists  of  short-rayed  stellate  cells 
found  in  all  the  layers;  of  long-rayed  cells  in  the  white  substance;  and  of 
peculiar  cells  with  small  bodies  at  the  outer  boundary  of  the  granular  layer 


CEREBELLUM 


431 


(Fig.  442).  These  send  only  a  few  short  processes  inward,  but  many 
long  processes  straight  out  to  the  free  surface,  where  they  end  in  triangular 
expansions.  In  this  way  a  thick  peripheral  neuroglia  layer  is  produced. 
As  long  as  the  cerebellar  cortex  is  not  fully  developed,  it  presents  a 
series  of  peculiarities  which  are  lacking  in  the  adult.  Thus  in  embryos 
and  young  animals  the  partly  developed  gray  stratum  is  covered  by  a 
superficial  granular  layer,  the  cells  of  which  later  become  more  deeply 
placed. 


a.t 


HEMISPHERES. 

The  ascending  sensory  fibers  from  the  thalamus  and  the  parts  below, 
and  the  descending  motor  fibers  which  pass  out  of  the  hemispheres  are 
contained  in  the  internal  capsule,  which  is  a  layer  of  white  substance  be- 
tween the  thalamus  medially  and  the  basal 
nuclei  of  the  hemispheres  laterally.  The  path 
by  which  these  fibers  enter  and  leave  the  deep 
white  substance  of  the  hemispheres  is  indi- 
cated in  Fig.  443.  Surrounding  the  inner 
white  substance  is  the  peripheral  layer  of  gray, 
which  forms  the  cerebral  cortex.  The  cortex 
is  divided  into  four  ill-defined  layers — an  outer 
molecular  or  neuroglia  layer;  a  layer  of  small 
pyramidal  cells;  a  layer  of  large  pyramidal 
cells;  and  next  the  white  substance,  a  layer  of 
polymorphous  cells.  From  the  pyramidal 
cells  the  fibers  of  the  descending  motor 
tract  arise.  The  layers  are  shown  in  Figs.  444  The  gray  substance  is  stippled;  the 

,  white  is  blank,     a.  t.,  Ascending 

and  445. 

The  molecular  layer,  which  in  ordinary  sec- 
tions appears  finely  punctate  or  reticular,  con- 
tains besides  many  neuroglia  cells,  a  network 
of  medulla  ted  tangential  fibers,  which  are  parallel  with  the  surface.  Other 
fibers,  as  shown  by  the  Golgi  method,  are  partly  neuroglia,  and  partly 
dendrites  of  pyramidal  cells.  The  "  cells  of  Retzius"  found  in  this  layer 
have  bodies  of  irregular  shape,  which  send  out  processes  parallel  with  the 
surface,  and  these  processes  send  short  branches  outward;  other  processes 
descend  into  the  deeper  layer  (Fig.  446).  They  are  probably  neuroglia 
cells. 

The  layer  of  small  pyramidal  cells  contains  a  special  form  of  nerve  cells, 
with  pyramidal  bodies  measuring  10-12  /*.  Since  they  taper  into  a  den- 
dritic process,  their  length  cannot  be  definitely  determined.  The  chief 
dendrite,  after  producing  small  lateral  branches,  enters  the  molecular  layer 


"d.t 


FIG.  443. — TRANSVERSE  SECTION  OF 
THE  BRAIN.  About  i  natural 
size. 


tract,  including  the  fillet;  c.  c., 
corpus  callosum;  d.  t.,  descending 
tract,  leaving  the  hemisphere  to 
enter  the  cerebral  peduncle;  n.  1., 
nucleus  lentif ormis ;  th.,  thalamus ; 
v.,  third  ventricle. 


432 


HISTOLOGY 


Supra 
radia 
network 


pyramidal 
cells. 


lupra-         '^3-77-^ '*-  -  -V  :>  *r*=  .'V- «  *J  B  b^>'<  • i^-? 
radial    -- 0% S^^S  ife^J ;^'  ^'  "^v 

.work.         :>  ,---^  ^  f-^h^rr:  ;  -- %  |  ^  ~%!  '-^ 


£^--^^)^\^^^.,^j^ 
*-:?C?.-^:"bL'^x:^:-Tr?i  f:^^'*-*  \*  fc^i5^| 


Inter- 
radial  --.. 
network. 


Radial 
bundles.    "•>*" 


Medulla 

or  white 

substance. 


Layer  of 

large 

pyramidal 
t  cells. 


Layerjjof 
polymor- 
phous 
nerve  cells. 


FIG.  445. 

FIGS.  444  and  445  are  from  verti< 
tions  of  the  cortex  (central  c< 
tion)  of  an  adult.  Fig.  444  is  a  1 
preparation;  Fig.  445  is  from  a  > 
stained  with  hsematoxylin  andi 
X  45- 


FIG.  444 


CEREBRAL    CORTEX 


433 


Cell  of  Retzius. 
Short-rayed  neuroglia  cell. 
Blood  vessel. 


---.   Small 

pyramidal 
cell. 


Large 

pyramidal 
cell. 


Collateral. 


Neuraxon  of  a 
polymophous 
nerve  cell. 


Long-rayed 
—          neuroglia 
cell. 


FIG.  446. — DIAGRAM  OF  THE  CEREBRAL  CORTEX.     The  cells  on  the  right  are  drawn  from  Golgi  prepara- 
tions of  an  adult  man.     X    120.     The  left  portion  of  the  diagram  is  X   60. 


where  it  arborizes  freely;  its  terminal  branches  often  show  small  irregular 
projections.  Lesser  dendrites  proceed  from  the  sides  and  basal  surface 
of  the  pyramidal  cell  body.  The  neuraxon  always  arises  from  the  basal 
surface,  and  after  producing  branched  collaterals,  it  generally  enters  the 
white  substance  where  it  may  divide  in  two  (Fig.  446,  3).  Sometimes  the 
neuraxon  turns  toward  the  molecular  layer,  joining  the  tangential  fibers; 
28 


434 


HISTOLOGY 


infrequently  an  inverted  pyramidal  cell  is  found.  The  neuraxons  and 
collaterals  are  medullated. 

The  layer  of  large  pyramidal  cells  contains  those  with  bodies  20-30  ^ 
long  (the  "giant  pyramidal  cells"  of  the  anterior  central  convolution 
measure  even  80  /*).  The  very  large  neuraxon  always  goes  to  the  white 
substance,  after  sending  out  several  collaterals  in  the  gray. 

The  layer  of  polymorphous  cells  includes  oval  or  polygonal  cells  which 
lack  a  chief  dendrite  directed  toward  the  surface;  their  slender  neuraxons 
produce  collaterals,  and  enter  the  white  substance  where  they  may  divide 
into  two  branches  in  T-form  (Fig.  446,  4).  Polymorphous  cells  with 
branched  neuraxons  limited  to  the  vicinity  of  the  cell  body,  are  found  in 
this  layer  and  in  the  pyramidal  layers  also.  The  neuraxon  may  branch  in 
the  molecular  layer  (Fig.  446,  6). 

Many  medullated  fibers  are  found  in  the  deeper  layers  of  pyramidal 
and  polymorphous  cells.  They  are  grouped  in  tapering  radial  bundles 
which  terminate  toward  the  layer  of  small  pyramidal  cells,  as  seen  in 
Fig.  444.  The  bundles  include  the  descending  medullated  neuraxons 
of  the  pyramidal  and  polymorphous  cells,  and  the  ascending  medullated 
sensory  fibers  from  the  white  substance.  The  latter  branch  repeatedly, 
forming  the  supra-radial  and  tangential  networks.  The  medullated  col- 
laterals of  the  pyramidal  cells  run  at  right  angles  with  the  radial  bundles; 
they  form  an  inter-radial  network,  the  outer  part  of  which  is  so  thick  in 
the  region  of  the  calcarine  fissure  that  it  can  be  seen  without  magnifica- 
tion,' and  is  there  known  as  the  "  stripe  of  Vicq  d'  Azyr."  Similar  bands 
may  be  detected  elsewhere  in  thick  sections  (Baillarger's  stripes). 

In  the  gyrus  hippocampi  and  gyrus  uncinatus  the  tangential  fibers 
are  so  abundant  as  to  form  a  considerable  layer,  the  sulstantia  reticularis 
alba.  The  hippocampus  (Ammon's  horn),  olfactory  bulb,  and  some  other 
areas  of  the  cortex,  differ  in  details  from  the  central  region  which  has  been 
described;  these  pecularities  are  considered  in  the  larger  special  works  on 
the  nervous  system. 

The  neuroglia  of  the  hemispheres,  like  that  of  the  cord,  is  at  first  a 
syncytium  with  strands  extending  from  the  ventricle  to  the  periphery. 
Later,  the  syncytium  is  divisible  into  short-rayed  neuroglia  cells  found 
chiefly  in  the  gray  substance,  long-rayed  cells  found  chiefly  in  the  white, 
and  ependymal  cells  lining  the  ventricles.  The  ependymal  layer  is  con- 
tinuous through  the  aqueduct  with  that  of  the  fourth  ventricle  and  central 
canal.  In  early  stages  its  cells  have  cilia-like  processes  which  are  in  part 
retained  in  the  adult.  The  short-rayed  cells,  which  are  characterized  by 
knotted,  branching  processes,  are  often  in  close  relation  with  the  blood 
vessels;  they  may  serve  to  transfer  the  nutritive  and  myelin-forming 
material  from  the  vessels  to  the  nerve  fibers.  The  outer  surface  of  the 
cerebral  cortex  is  covered  with  a  feltwork  of  neuroglia  fibers. 


HYPOPHYSIS  435 

HYPOPHYSIS. 

The  hypophysis  (i.e.,  a  growth  beneath  the  brain)  is  a  rounded  mass, 
about  half  an  inch  wide  and  a  quarter  of  an  inch  thick,  attached  to  the 
tip  of  the  infundibulum,  and  lodged  in  the  sella  turcica  of  the  sphenoid 
bone.  Its  stalk  of  attachment  to  the  infundibulum  extends  through  the 
fibrous  membrane  fastened  to  the  four  posts  or  corners  o£  the  sella,  and 
in  removing  the  brain,  the  hypophysis  is  therefore  often  torn  from  its 
stalk  and  left  in  the  bony  excavation.  It  is  now  known  to  be  a  most 
important  organ  of  internal  secretion,  consisting  of  two  parts  which  are  as 
distinct  from  one  another  as  the  cortex  and  medulla  of  the  suprarenal 
gland.  The  anterior  lobe  is  formed  from  Rathke's  pouch  (Rathke,  Arch.  f. 
Anat.,  Phys.,  u.  wiss.  Med.,  1838,  pp.  482-485)  which  grows  upward  from 
the  oral  ectoderm  and  encounters  the  knob-like  posterior  lobe  which  is'a 
part  of  the  brain  (Fig.  203,  p.  216).  The  anterior  lobe  then  sends  up  a 
short  process  on  either  side  of  the  posterior  lobe,  like  the  thumb  and  first 
finger  of  a  hand,  and  in  later  stages  Gushing  ventures  to  describe  the  pos- 


FIG.  447. — DIAGRAMS  OF  THE  HYPOPHYSIS  CEREBRI.     (From  Morris's  Anatomy,  after  Testut.) 

A,  Posterior  surface.     B,  Transverse  section.     C,  Sagittal  section.     I,  Anterior  lobe;  2,  posterior  lobe; 

3,  infundibulum;  4,  optic  chiasma;  5,  infundibular  recess;  6,  optic  recess. 

terior  lobe  as  resting  in  the  anterior  lobe  like  a  ball  in  a  catcher's  glove. 
The  anterior  lobe  becomes  separated  from  the  roof  of  the  mouth  by  the 
obliteration  of  its  duct,  which  is  reduced  to  a  slender  solid  epithelial  strand 
and  ruptures  in  embryos  of  about  20  mm.  A  depression  marking  its  former 
outlet  has  sometimes  been  found  in  the  vault  of  the  pharynx,  and  there 
may  be  a  canal  through  the  sphenoid  bone,  the  craniopharyngeal  canal, 
which  follows  the  course  of  the  former  duct.  It  is  said  that  a  small 
"pharyngeal  hypophysis,"  having  the  structure  of  the  anterior  lobe,  is 
constantly  found  near  the  pharyngeal  end  of  this  canal,  on  the  under 
surface  of  the  sphenoid  bone. 

The  posterior  surface  of  both  lobes,  as  they  appear  in  the  adult,  is 
shown  in  Fig.  447,  A,  and  a  sagittal  section  is  shown  in  C;  the  orientation 
of  the  latter  may  readily  be  understood  by  comparing  it  with  the  region 
of  the  optic  recess  in  Fig.  434. 

The  hypophysis  can  hardly  be  overlooked  in  examining  the  brain,  and  its  existence 
is  recorded  by  the  earliest  writers.  The  epiphysis,  on  the  top  of  the  brain,  was  called 


436 


HISTOLOGY 


the  pineal  body  from  its  resemblance  to  a  pine  cone,  and  according  to  Hyrtl  the  hypo- 
physis below,  being  a  round  structure  attached  to  a  stem,  was  named  the  "rose  hip" 
by  the  Mohammedan  physician  Avicenna  (ca.  A.  D.  1000).  Vesalius  introduced 
the  name  pituitary  gland.  The  pituita  or  phlegm  was  believed  to  be  excrementitious 
material,  eliminated  by  the  brain  and  received  by  the  naso-pharynx,  and  its  possible 
origin  by  way  of  the  olfactory  nerves  had  been  discussed.  Vesalius  and  his  followers 
believed  that  it  was  collected  by  the  infundibular  funnel  and  eliminated  by  the  pituitary 
gland.  If  the  sella  turcica  of  a  prepared  skull  is  examined,  four  grooves  may  be  traced 
from  it,  two  passing  forward  to  the  optic  foramina,  and  two  passing  backward  to  the 
lacerated  foramina.  Vesalius  pictured  these  four  channels  as  outlets  for  the  pituitary 
gland,  the  two  latter  (which  in  life  are  closed  by  cartilage)  being  in  relation  with  the 
naso-pharynx.  Bartholin  recorded  another  function  of  the  pituitary  gland,  namely, 
"to  close  the  infundibulum  lest  vital  spirits  should  escape,"  and  finally  V.  C.  Schneider 
showed  conclusively  that  the  pituitary  gland  is  not  the  source  of  phlegm.  According 
to  Hyrtl  this  was  accomplished  in  five  classic  but  lengthy  books,  De  catarrhis,  1640- 
1642,  and  he  adds — "No  physician  and  no  anatomist  should  leave  this  fundamental 
and  learned  work  unread — if  he  has  time  for  it." 

The  anterior  lobe  consists  of  solid  branched  epithelial  cords,  of  irregular 
caliber,  connected  with  one  another  by  frequent  anastomoses.     Between 


Portion  of  the 
anterior  lobe. 


Portion  of  the 
posterior  lobe. 


Epithelial  cord. 


-  Epithelial  follicle. 


Blood  vessel  con- 
taining blood 
corpuscles. 

"*_-.        "Colloid" 
substance. 


Multipolar  cell. 


Connective  tissue' 
fibers. 


FIG.  448. — PORTION  OF  A  HORIZONTAL  SECTION  OF  A  HUMAN  HYPOPHYSIS,  showing  the  boundary  line 
between  the  anterior  and  the*  posterior  lobes.  Two  gland  follicles  on  the  left  each  contain  a  dark 
epithelial  cell.  X  220. 

the  cords  and  in  close  relation  with  them,  there  are  wide  lacunar  capil- 
laries derived  from  several  arterioles  which  descend  along  the  stalk  of  the 
infundibulum.  The  wide  terminal  vessels  are  arterio- venous  connections 
having  a  sinusoidal  structure.  Along  their  margins,  especially  in  the 
central  part  of  the  lobe,  the  cords  are  covered  with  eosinophilic  cells, 
having  round  nuclei;  the  axial  cells  of  the  cords  are  neutrophilic  and  less 
granular.  Although  the  nature  of  the  marginal  cells  has  not  been 
fully  determined,  they  are  usually  described  as  glandular,  and  their  gran- 
ules presumably  represent  an  internal  secretion  which  is  discharged  into 
the  adjacent  vessels.  At  the  periphery  of  the  anterior  lobe,  basophile 
cells  occur. 


HYPOPHYSIS 


437 


Like  the  cortex  of  the  suprarenal  gland,  the  anterior  lobe  of  the  hypophysis  is  the 
larger  part,  and  has  a  characteristic  epithelial  structure,  whereas  the  portion  associated 
with  the  nervous  system  is  smaller,  with  less  striking  morphological  characters.  Never- 
theless the  latter,  in  both  cases,  produces  the  more  active  extracts,  and  its  products  are 
better  understood.  The  anterior  lobe  of  the  hypophysis  appears  to  "preside  more 
intimately  over  skeletal  growth;"  and  overgrowth,  acromegaly  and  gigantism  are  at- 
tributed to  its  excessive  activity.  The  administration  of  extracts  of  the  posterior  lobe 
causes  a  rise  in  blood  pressure,  owing  to  the  contraction  of  the  vascular  musculature, 
,thus  resembling  adrenalin  in  its  action.  Repeated  injections  cause  emaciation;  and 
deficient  secretion,  or  the  removal  of  the  gland,  leads  to  a  high  tolerance  for  sugars 
with  the  resultant  accumulation  of  fat.  "Thus  normal  activity  of  the  posterior  lobe 
is  essential  for  effective  carbohydrate  metabolism"  (Gushing,  The  Pituitary  Gland  and 
its  Disorders,  1912). 

The  posterior  lobe  consists  of  a  mass  of  neuroglia  cells,  the  pars  nervosa, 
and  an  epithelial  investment,  the  pars  intermedia.  The  latter  is  of  special 
interest  since  its  cells,  sometimes  ciliated, .  tend  to  become  arranged  in 
cysts  containing  a  hyaline  or  colloid  secretion.  According  to  Stohr,  these 
cysts  belong  with  the  anterior  lobe,  and  since  the  two  lobes  are  in  contact 
near  the  anterior  part  of  the  infundibular  stalk,  it  is  possible  that  its  ele- 
ments have  grown  around  and  invested  the  pars  nervosa,  thus  producing 
the  pars  intermedia.  Except  anteriorly,  however,  the  two  lobes  of  the 
hypophysis  are  generally  separated  by  a  cleft. 

The  pars  nervosa  contains  ependymal  and  neuroglia  cells,  but  no 
nerve  cells  and  only  a  few  nerve  fibers.  The  ependyma  lines  the  cavity 
which  extends  downward  into  the  lobe  from  the  inf  undibulum.  According 
to  Tilney,  "very  often  in  the  human  hypophysis  the  lumen  is  not  only  seen 
to  be  distended  by  large  masses  of  colloid,  but  its  walls  are  evaginated  so 
as  to  give  rise  to  cysts  of  varying  sizes,  all  containing  colloid"  (Mem.  of 
the  Wistar  Inst,  No.  2,  1911).  The  colloid  material  is  believed  to  be 
evidence  of  a  secretion  which  is  eliminated  into  the  third  ventricle,  and 
which  finds  its  way  into  the  cerebro-spinal  fluid.  Possibly  it  may  be  given 
off  from  the  outer  surface  of  the  lobe,  for  the  inconstant  cavity  or  lumen 
is  not  a  typical  duct;  but  the  secretion  apparently  does  not  enter  the  blood 
vessels,  which  in  this  lobe  are  neither  abundant  nor  sinusoidal.  Eosino- 
philic  cells  are  generally  absent. 

PINEAL  BODY. 

The  pineal  body  (sometimes  called  the  epiphysis)  is  a  median  dorsal 
outpocketing  of  the  diencephalon  (Figs.  434  and  435),  terminating  in  a 
small  nodule  composed  of  neuroglia  and  round  or  polygonal  epithelial 
cells.  The  human  pineal  body  contains  no  nerves  (Kolliker)  but  below  it 
there  is  the  commissura  habenularum.  A  connective  tissue  capsule  sends 
prolongations  into  its  interior  and  surrounds  groups  of  epithelial  cells,  and 
follicles. 


438  HISTOLOGY 

It  is  generally  considered  that  the  pineal  body  is  a  functionless  rudi- 
ment. In  lower  vertebrates  an  eye-like  structure  develops  just  in  front  of 
it,  sometimes  being  found  beneath  a  transparent  cornea,  but  the  extent 
of  the  visual  functions  of  this  organ  remains  undetermined.  The  corpus 
pineale  immediately  behind  this  eye  may  take  its  place  to  some  extent, 
and  "  of  ten  shows,  as  in  certain  lizards,  traces  of  visual  structure" 
(Kingsley).  The  unimportant  position  to  which  this  organ  has  been 
relegated,  contrasts  with  the  familiar  conjecture  of  Des  Cartes  that  all 
ideas  which  proceed  from  the  five  senses  are  perceived  in  the  pineal  body 
as  a  center,  and  that  from  it  all  nervous  impulses  irradiate.  In  man  not 
the  slightest  function  is  now  assigned  to  it. 

Within  the  pineal  body,  acervulus  cerebri  or  "  brain 
sand"  is  usually  found,  consisting  of  round  or  mul- 
berry-like concretions,  5  /*  to  i  mm.  in  diameter  (Fig. 
449).  In  specimens  preserved  in  glycerin  or  balsam 
these  concretions  show  distinct  concentric  layers.  They 
consist  of  an  organic  matrix  containing  calcium  carbo- 
nate and  magnesium  phosphate,  and  are  sometimes 
FIG.  449-AcERvuLus  surrounded  by  a  thick  connective  tissue  capsule. 

BODYO?AWONMAN          Not  infrequently,  especially  in  old  age,  the  brain 

OLDENTX  soYEARS     substance  contains  round  or  elongated  bodies,  distinctly 

stratified,  which  are  colored  violet  by  tincture  of  iodine 

and   sulphuric  acid,  and  therefore  are  related  to  amyloid.     These  cor- 

puscula  amylacea  are  found  almost  always  in  the  walls  of  the  ventricles, 

and  also  in  many  other  places  in  both  gray  and  white  substance,  and 

in  the  optic  nerve.     They  have  a  homogeneous  capsule  with  occasional 

processes,   and   are   evidently   neuroglia  cells  transformed  by  amyloid 

infiltration. 


MENINGES. 

The  dura  mater  cerebralis  or  dura  mater  of  the  brain,  includes  the 
periosteum  of  the  inner  surface  of  the  cranium  and  consists,  therefore,  of 
two  lamellae.  The  inner  is  like  the  dura  mater  of  the  cord  but  contains 
more  elastic  fibers;  the  outer  corresponds  with  the  periosteum  of  the  verte- 
bral canal.  It  contains  the  same  elements  as  the  inner  layer,  but  its  fibers 
run  in  a  different  direction.  In  order  that  the  dura  of  the  brain  and  cord 
may  be  strictly  comparable,  some  anatomists  count  the  vertebral  perios- 
teum and  the  considerable  layer  of  vascular  fatty  tissue  beneath  it,  as 
a  part  of  the  dura  of  the  cord.  In  relation  with  the  brain,  the  dura  forms 
reduplications  extending  between  the  cerebellum  and  the  hemispheres, 
and  between  the  right  and  left  hemispheres.  Its  two  layers  separate  to 
enclose  large,  thin- walled  veins,  the  sinuses  of  the  dura.  These  receive 


MENINGES  439 

veins  from  the  substance  of  the  brain,  but  the  arteries  of  the  dura,  or 
meningeal  arteries,  supply  the  cranial  periosteum.  The  dura  has  many 
nerves,  some  with  free  endings,  and  others  supplying  the  musculature  of 
the  vessels. 

The  arachnoid  membrane,  as  in  the  cord,  is  separated  from  the  dura 
by  a  cleft-like  sub-dural  space.  In  certain  places,  especially  along  the 
sides  of  the  superior  sagittal  sinus,  there  are  found  arachnoid  villi  (Pac- 
chionian  bodies  or  granulations),  which  project  into  the  cavity  of  the  ven- 
ous sinus.  They  are  elevations  of  the  arachnoid  covered  with  a  thin  por- 
tion of  the  dura  and  venous  endothelium,  and  possibly  facilitate  the  trans- 
fer of  fluid  between  the  arachnoid  (or  subarachnoid)  spaces  and  the  veins. 
These  spaces  contain  the  cerebro-spinal  fluid,  and  are  continuous  with 
the  corresponding  spaces  around  the  cord.  Through  apertures  in  the 
thin  roof  of  the  fourth  ventricle,  they  communicate  with  the  central 
cavity  of  the  cord  and  brain. 

The  pia  is  a  delicate  and  highly  vascular  layer,  containing  arteries 
which  send  branches  into  the  cortex  from  all  points  on  its  surface.  These 
cortical  arteries  arise  from  the  anastomoses  between  the  internal  carotid 
and  vertebral  arteries  at  the  base  of  the  brain,  which  produce  the  arterial 
circle  of  Willis.  Other  branches  from  these  vessels  enter  the  substance  of 
the  base  of  the  brain,  supplying  the  basal  nuclei,  thalamus  and  internal 
capsule.  Because  of  the  effects  of  haemorrhage  in  relation  with  the  motor 
and  sensory  tracts  in  this  region,  these  small  arteries  are  of  very  great 
importance.  The  vascular  membranes  which  cover  the  thin  portions  of 
the 'roof  of  the  third  and  fourth  ventricles  are  in  places  invaginated  into 
the  ventricles,  forming  the  chorioid  plexuses.  These  networks  of  small 
vessels,  covered  only  by  thin  membranes,  are  found  in  the  lateral  ven- 
tricles, as  well  as  in  the  third  and  fourth;  their  position  is  described  in 
text-books  of  gross  anatomy.  The  simple  layer  of  cuboidal  epithelium, 
which  covers  the  plexuses,  contains  pigment  granules  and  fat  droplets, 
and  may  perform  secretory  functions. 

EYE. 

Development  and  General  Anatomy.  The  eyes  first  appear  as  a  pair  of 
optic  vesicles,  which  are  lateral  out-pocketings  of  the  fore-brain  (Fig. 
451,  A).  They  enlarge  rapidly,  but  their  connections  with  the  wall  of 
the  brain  remain  relatively  slender,  forming  the  optic  stalks.  The  epi- 
dermal ectoderm  immediately  overlying  the  vesicles  thickens  and  be- 
comes invaginated  (Fig.  451,  B  and  C).  The  invaginated  portion  is  then 
detached  in  the  form  of  a  vesicle,  the  inner  wall  of  which  is  distinctly 
thicker  than  the  outer;  this  "lentic  vesicle"  becomes  the  lens  of  the  eye. 
Meanwhile,  as  seen  in  B  and  C,  that  layer  of  the  optic  vesicle  which  is 


440  HISTOLOGY 

toward  the  epidermis  sinks  in  upon  the  deeper  layer,  transforming  the 
vesicle  into  the  optic  cup.  At  first  the  cup  is  not  complete,  being  deficient 
on  its  lower  side  (Fig.  450).  The  arteria  centralis  retina  is  seen  passing 
through  this  indentation,  which  begins  on  the  lower  surface  of  the  stalk 
and  extends  to  the  free  margin  of  the  cup;  the  cleft  is  sometimes  called 
the  "chorioid  fissure."  Distal  to  the  point  of  entrance  of  the  artery  into 
the  optic  cup,  the  edges  of  the  fissure  fuse;  the  artery  then  appears  to 
perforate  the  base  of  the  cup,  and  it  retains  this  relation  in  the  adult. 
The  artery  is  shown  in  section  in  Fig.  451,  D. 

In  a  remarkable  series  of  experiments  upon  tadpoles,  Warren  Lewis  has  shown 
that  "the  lens  is  dependent  for  its  origin  on  the  contact  influence  or  stimulus  of  the 
optic  vesicle."  If  the  optic  vesicle  is  removed,  the  epithelium  in  the  region  of  the 
normal  lens  does  not  become  thickened  or  invaginated;  but  if  an  optic  vesicle  is 
transplanted  by  detaching  it  from  its  stalk  and  pushing  it  caudally  through  the 
mesenchyma,  it  will  cause  the  formation  of  a  lens  from  any  portion  of  the  epidermal 
epithelium  which  happens  to  be  above  it.  Moreover,  if  an  area  of  skin  from  the  ab- 
domen of  a  frog  of  one  species  is  grafted  over  the  optic  vesicle  of  another  species,  a 
lens  may  be  produced  from  the  grafted  epithelium.  Thus  there  is  no  predetermined 
area  for  lens  formation,  and  its  development  depends  upon  the  presence  of  the  vesicle 
beneath  (Amer.  Journ.  Anat.,  1904,  vol.  3,  pp.  505-536,  1907,  vol.  7,  pp.  145-169). 

The  two  layers  of  the  optic  cup,  the  inner  of 
which  is  toward  the  lens,  are  normally  in  contact 
with  one  another,  although  in  sections  they  have 
often  become  more  or  less  separated.  They  consti- 
tute the  retina,  which  includes  a  thin  outer  pig- 
mented  layer,  and  a  thick  inner  visual  layer;  the 
FIG.  450.— OPTIC  CUP  AND  latter  is  composed  of  several  strata  of  nerve  cells  and 

oTALK     OF     A     HUMAN 

F/ft?rYKoSLann.)  MM'  nbers-  Tne  stimulus  of  light  is  received  by  tapering 
projections  extending  from  the  outer  surface  of  the 
visual  layer  toward  the  pigmented  layer;  to  reach  them  the  rays  of 
light  must  traverse  the  strata  of  the  visual  layer.  In  explanation  of 
the  fact  that  the  sensory  processes  are  turned  away  from  the  light,  it 
may  be  said  that  the  outer  surface  of  the  skin  ordinarily  receives  stimuli, 
and  that  through  the  infolding  which  makes  the  medullary  tube  and  the 
outpocketing  which  makes  the  optic  vesicle,  the  sensory  surface  of  the 
retina  is  continuous  with  the  outer  surface  of  the  skin.  Since  in  mammals 
the  optic  vesicles  begin  to  form  before  the  related  portion  of  the  medullary 
groove  has  closed,  they  first  appear  as  depressions  in  a  thickened  epidermal 
ectoderm. 

Nerve  fibers  grow  from  the  inner  surface  of  the  visual  layer  toward 
the  central  artery  and  vein  of  the  retina,  around  which  they  pass  out  of 
the  optic  cup  (Fig.  451,  D).  They  grow  beneath  and  among  the  cells  of 
the  optic  stalk  to  the  brain,  which  they  enter.  These  fibers,  which  con- 
stitute the  optic  nerve,  cause  the  obliteration  of  the  optic  stalk.  It  is 


EYE 


441 


shown  in  the  figure  that  the  optic  nerve  at  its  origin  interrupts  the  retinal 
layers,  producing  a  "blind  spot."  The  part  of  the  nerve  which  forms  the 
blind  spot,  with  the  vessels  in  its  center,  is  called  the  papilla  of  the  optic 
nerve. 

The  lens  (Fig.  451,  D)  loses  its  central  cavity  by  the  elongation  of  the 
cells  in  its  posterior  layer.  These  become  the  fibers  of  the  lens.  The 
anterior  layer  remains  throughout  life  as  a  simple  epithelium,  called  the 
epithelium  of  the  lens.  The  lens  becomes  covered  by  an  elastic  capsula 


c.p. 
conj. 

FIG.  451. — ^SECTIONS  OF  RABBIT  EMBRYOS  TO  SHOW  THE  DEVELOPMENT  OF  THE  EYE.  A,  9$  days,  3.0  mm.; 
B,  io|  days,  5.4  mm.;  C,  n  days,  5.0  mm.;  D,  14  days,  18  hours,  12.0  mm.;  E,  20  days,  29  mm. 

a.  c.  r.,  Arteria  centralis  retinae;  c.,  cornea;  c.  a.,  anterior  chamber;  conj.,  conjunctiva;  c.  p.,  posterior 
chamber;  c.  v.,  corpus  vitreum;  e.  1.,  eyelid;  f.  b.,  fore-brain;  1.,  lens;  1.  e.,  lens  epithelium;  1.  f.,  lens 
fibers;  o.  c.,  optic  cup;  o.  n.,  optic  nerve;  o.  v.,  optic  vesicle;  r.  p.,  pigmented  layer  of  the  retina;  r.  v., 
visual  layer  of  the  retina. 

lentis,  and  in  embryonic  life  it  possesses  a  vascular  capsule  (Fig.  451,  E) 
containing  branches  of  the  central  artery.  The  vascular  layer  covering 
the  anterior  surface  of  the  lens  is  designated  the  pupillary  membrane,  and 
it  disappears  shortly  before  birth.  Its  occasional  persistence  interferes 
with  vision. 

Between  the  lens  and  the  retina  there  is  a  peculiar  tissue,  mucoid  in 
appearance  and  resembling  mesenchyma  in  form.     Since  processes  from 


442  HISTOLOGY 

the  retina  and  from  the  lens  have  been  found  extending  into  it,  it  is  con- 
sidered to  be  essentially  ectodermal.  Its  blood  vessels  become  obliter- 
ated and  it  forms  the  vitreous  body  of  the  adult,  consisting  of  a  stroma  and 
a  humor.  Extending  through  it,  from  the  papilla  of  the  optic  nerve  toward 
the  lens,  is  the  hyaloid  canal,  which  in  the  embryo  lodged  the  hyaloid 
artery  (a  prolongation  of  the  central  artery).  Sometimes  this  artery  is 
represented  in  the  adult  by  a  strand  of  tissue.  The  vitreous  body  is 
surrounded  by  a  fibrous  layer  called  the  hyaloid  membrane. 

A  cavity  forms  in  the  tissue  in  front  of  the  lens  and  becomes  filled  with 
a  watery  tissue  fluid  (aqueous  humor).  It  is  bounded  by  a  mesen- 
chymal  epithelium.  The  portion  of  the  cavity  which  is  anterior  to  the 
retinal  cup  and  lens  is  called  the  anterior  chamber  of  the  eye;  the  smaller 
part  within  the  retinal  cup  but  in  front  of  the  lens  and  the  fibrous  covering 
of  the  vitreous  body,  is  the  posterior  chamber  (Fig.  451,  E,  c.p.). 

The  retinal  cup  is  surrounded  by  two  layers  of  mesenchymal  origin. 
The  inner  tunica  vasculosa  corresponds  with  the  pia  mater  and  forms  the 
chorioid  coat  of  the  eye;  the  outer  tunica  fibrosa  corresponds  with  the 
dura  mater  and  forms  the  sclera,  into  which  the  muscles  of  the  eye  are 
inserted.  The  portion  of  the  retinal  cup  which  forms  a  curtain,  circular 
in  front  view,  between  the  anterior  and  posterior  chambers,  is  called  the 
iris.  It  consists  of  tunica  vasculosa  with  a  thin  pigmented  prolongation 
of  the  retina  over  its  posterior  surface  (Figs.  451,  E,  and  452).  This  pars 
iridica  retina  is  rudimentary  and  without  visual  function.  The  iris  is 
covered  by  the  mesenchymal  epithelium  of  the  chambers.  At  the  at- 
tached border  of  the  iris  the  vascular  coat  contains  important  muscle 
fibers,  and  is  there  thickened  to  form  the  ciliary  body.  This  is  also  covered 
by  a  rudimentary  pigmented  layer  on  its  inner  surface,  the  pars  ciliaris 
retina.  At  the  or  a  serrata  (Fig.  467)  an  abrupt  thickening  of  the  visual 
layer  of  the  retina  marks  the  boundary  between  its  ciliary  and  optic 
portions.  The  pars  optica  retina  extends  from  the  ora  to  the  optic 
nerve,  covered  externally  by  the  chorioid  and  sclera. 

As  a  relatively  frequent  congenital  anomaly,  the  chorioid  fissure  fails  to  close 
normally  and  the  resulting  defect  is  known  as  coloboma.  If  the  closure  has  been 
nearly  complete,  so  that  there  is  merely  a  notch  at  the  free  margin  of  the  optic  cup, 
it  appears  in  the  adult  as  a  median  ventral  cleft  in  the  iris,  so  that  the  pupil  is  shaped 
like  an  inverted  pear.  If  the  deeper  parts  of  the  chorioid  fissure  fail  to  unite,  there 
will  be  a  median  ventral  gap  in  the  optic  portion  of  the  retina,  which  may  seriously 
interfere  with  vision. 

The  cornea  is  the  tissue  in  front  of  the  anterior  chamber,  consisting  of 
a  non-vascular  mesenchymal  tissue,  bounded  posteriorly  by  mesenchymal 
epithelium  and  anteriorly  by  the  epidermal  ectoderm.  It  is  extremely 
transparent.  The  epidermal  ectoderm  extends  from  the  cornea  and  front 
of  the  eye  over  two  folds  which  form  the  eyelids.  They  have  met  in 


EYE 


443 


Fig.  451,  D,  and  fused  temporarily.  Externally  the  lids  are  covered  by 
skin,  and  internally  by  the  conjunctiva  palpebrarum,  or  conjunctiva  of  the 
lids.  The  latter  is  continuous  with  the  conjunctiva  bulbi  which  forms 
the  opaque  vascular  "  white  of  the  eye."  It  surrounds  the  cornea,  the 
epithelium  of  the  two  structures  being  continuous. 

The  parts  of  the  eye  to  be  examined  histologically  are  therefore  the 
retina,  optic  nerve,  lens,  and  vitreous  body,  all  of  which  are  ectodermal; 


Epithelium 
Anterior  basal  lamina 
Substantia  propria 
Posterior  basal  lamina 

Mesenchymal  epithelium 


of  the  cornea. 


Sphincter  muscle 
,  Stroma 

Pars  iridica  retinae 
Angle  of  the  iris. 


of  the  iris. 


Sinus  venosus  sclerae 


Epithelium  1  of  the 

~     .  L  conjunctiva 

Tunica          f  bulbi 

propria     J 


Zonula.     Ciliary  process     muscle  fibers. 


Capsule 

'    Epithelium       \  of  the  lens. 
Fibers 


Circular  Meridional  Pars  ciliaris  retinae. 


FIG.  452. — MERIDIONAL  SECTION  OF  A  PART  OF  THE  EYE.     X  15. 
The  radial  fibers  of  the  ciliary  muscle  cannot  be  distinguished  with  this  magnification. 

then  the  tunica  vasculosa,  including  the  chorioid,  the  ciliary  body,  and 
iris;  next  the  tunica  fibrosa,  including  the  sclera  and  cornea;  and  finally 
the  accessory  structures — the  lids,  conjunctivas  and  glands. 


RETINA. 

The  retina  extends  from  the  papilla  of  the  optic  nerve  to  the  pupillary 
border  of  the  iris,  and  is  divisible  into  three  parts;  the  pars  optica  retina 
includes  -all  which  is  actually  connected  with  the  optic  nerve  and  which 
therefore  is  sensitive  to  light.  It  covers  the  deeper  portion  of  the  optic 


444 


HISTOLOGY 


cup,  ending  near  the  ciliary  body  in  a  macroscopic,  sharp,  irregular  line 
bounding  the  ora  serrata.  The  pars  ciliaris  and  the  pars  iridica  retina 
are  the  rudimentary  layers  covering  the  ciliary  body  and  iris  respectively. 
The  pars  optica  retinae  in  a  fresh  condition  is  a  transparent  layer 
colored  reddish  by  the  "visual  purple."  In  sections  it  presents  many 
layers  arranged  as  seen  in  Fig.  453,  the  cells  of  which  are  related  to  one 
another  as  in  the  diagram,  Fig.  454.  The  outer  layer  of  the  optic  cup 
forms  the  pigmented  epithelium  of  the  retina,  which  consists  of  a  simple 
layer  of  six-sided  cells.  Toward  their  outer  surface  (that  next  the  chorioid, 
where  the  nucleus  lies)  they  are  poor  in  pigment,  whereas  in  their  inner 
portion  they  contain  numerous  rod-shaped  (1-5  n  long)  brown  granules  of 


Chorioid. 

Pigmented  _ 
epithelium. 

Layer  of  rods  and  I 
cones. 


Membrana  limitans  — 
externa. 


Outer  nuclear 
layer. 

Henle's  fiber  layer. 

Outer  reticular 
layer. 

Inner  nuclear  I 
layer.  j 

Inner  reticular  I 
layer. 


Ganglion  cell  layer. 
Nerve  fiber  layer. 

Membrana  limitans 
interna. 


MJ-^i2 


.Vessels    of     the 
choriocapil- 
laris. 
Lamina  basalis. 


~  Rods     \  Outer. 

-  Cones    J  segment. 

-  Cones 


Rods 


Inner 
segment. 


Base  of  a  cone  fiber. 


Nucleus  of  a  radial 
fiber. 


Nucleus  of  an 
amakrine  cell. 


Pyramidal  base  of 
a  radial  fiber. 


Blood  vessels. 


FIG.  453. — VERTICAL  SECTION  OF  A  HUMAN  RETINA.     X  36. 

the  pigment  "  fuscin."  In  albinos  the  pigment  is  lacking.  From  the  inner 
surface  of  the  pigmented  epithelium,  numerous  processes  extend  between 
the  rods  and  cones. 

The  visual  cells,  which  are  found  along  the  outer  surface  of  the  inner 
retinal  layer,  are  of  two  sorts,  rod  cells  and  cone  cells.  In  both,  the  nucleus 
is  found  in  the  inner  half  of  the  cell,  and  the  outer  non-nucleated  half 
projects  through  a  membrane,  the  membrana  limitans  externa.  This 
causes  the  visual  cells  to  appear  divided  into  layers,  their  nucleated 
parts  beneath  the  limiting  membrane  constituting  the  outer  nuclear  layer 
(or  outer  granular  layer),  and  the  non-nucleated  parts  outside  of  the 
membrane  forming  the  layer  of  rods  and  cones. 

The  rods  are  four  times  as  numerous  as  the  cones.  They  are  regularly 
placed  so  that  three  or  four  rods  are  found  between  every  two  cones  (Fig. 


EYE 


445 


453).  The  rods  are  elongated  cylinders  (60  /*  long  and  2  ^  thick)  consisting 
of  a  homogeneous  outer  segment,  in  which  the  visual  purple  is  found 
exclusively,  and  a  finely  granular  inner  segment.  In  the  outer  third  of 
the  inner  segment  there  is  said  to  be  an  ellipsoidal,  vertically  striated 
structure  (which  in  some  lower  vertebrates  is  very  distinct).  The  por- 
tion of  the  rod  cells  below  the  limiting  membrane  is  a  slender  thread, 
expanding  to  surround  the  nucleus  which  is  characterized  by  from  one 
to  three  transverse  bands.  Beneath. the  nucleus  the  protoplasm  again 
becomes  thread-like,  and  this  basal  prolongation  of  the  cell  terminates 
in  a  small  club-shaped  enlargement,  without  processes  (Fig.  454). 


Cone  cell.    -~ 
Rod  cell,    ---*$- 

Stellate  ganglion  cell.  , 
Bipolar  cells. 

Amakrine  cells.  *" 
Centrifugal  nerve  fiber.  -- 

Multipolar  ganglion  cell.    - 


ii      Layer  of  rods  and  cones. 
jJL*  Membrana  limitans 

m  externa' 

OQ-f'  Outer  nuclear  layer. 


f;  Henle's  fiber  layer. 
•<  Outer  reticular  layer. 

uclear  layer. 


Inner  reticular  layer. 

Ganglion  cell  layer. 
Nerve  fiber  layer. 


Collateral. 


Pyramidal  bases 
of  radial  fibers. 


FIG.  454. — DIAGRAM  OF  HUMAN  RETINA.     SUPPORTING  SUBSTANCE  RED. 

The  cones  likewise  consist  of  an  outer  and  an  inner  segment.  The 
conical  outer  segments  are  shorter  than  those  of  the  rods.  The  inner 
segments  are  thick  and  somewhat  dilated  so  that  the  entire  cone  is  flask- 
shaped.  Moreover,  the  inner  segment  contains  a  vertically  striated 
" fiber  apparatus/7  The  nuclei  of  the  cone  cells  are  situated  just  beneath 
the  limiting  membrane;  below  the  nuclei  the  protoplasm  forms  a  fiber,  end- 
ing in  an  expanded  pyramidal  base. 

The  entire  visual  cells  therefore  form  three  layers  of  the  retina,  namely, 
(i)  the  layer  of  rods  and  cones;  (2)  the  outer  nuclear  layer,  containing  the 
nuclei  of  the  rod  and  cone  cells;  and  (3)  Henle's  fiber  layer,  composed 
of  the  basal  processes  of  these  cells.  The  three  layers  next  beneath  are 
formed  essentially  of  superposed  parts  of  the  radially  arranged  bipolar 
nerve  cells,  which  constitute  the  ganglion  retina.  Immediately  beneath 
Henle's  fiber  layer,  dendritic  processes  of  these  cells  form  an  outer  reticular 
layer,  whereas  their  nuclei  are  situated  in  an  inner  nuclear  layer,  and  their 
centripetal  processes,  or  neuraxons,  enter  an  inner  reticular  layer.  There 


446  HISTOLOGY 

they  terminate  in  relation  with  dendrites  and  cell  bodies  of  large  ganglion 
cells  which  consitute  the  ganglion  of  the  optic  nerve.  Cell  bodies  of  this 
ganglion  form  the  ganglion  cell  layer,  and  their  neuraxons,  traveling  toward 
the  papilla  of  the  optic  nerve,  are  the  principal  elements  in  the  nerve  fiber 
layer.  The  latter  is  separated  from  the  vitreous  body  by  an  internal 
limiting  membrane.  Thus  visual  stimuli,  received  by  the  rods  and  cones, 
are  transferred  by  means  of  the  bipolar  cells  of  the  ganglion  retinae,  to  the 
ganglion  cells  of  the  optic  nerve,  .through  the  neuraxons  of  which  they 
proceed  to  the  brain.  These  layers  may  be  described  in  further  detail  as 
.follows : 

Henle's  fiber  layer  contains  not  only  the  fiber-like  basal  ends  of  the 
rod  and  cone  cells,  but  also  the  slender  unbranched  dendritic  processes 
of  the  bipolar  cells  of  the  ganglion  retinae.  Each  bipolar  cell  sends  one 
such  process  through  Henle's  layer  to  terminate  in  a  little  thickening 
near  the  membrana  limitans  externa.  In  the  outer  reticular  layer,  how- 
ever, these  dendrites  of  the  bipolar  cells  send  out  branches  which  bifurcate 
repeatedly,  becoming  reduced  to  the  finest  fibrils;  they  form  a  close  sub- 
epithelial  felt- work  (Fig.  454). 

Occasionally  nuclei  are  found  in  the  outer  reticular  layer.  Most  of 
these  belong  with  bipolar  cells  displaced  outward  (Fig.  454,  x).  Toward 
the  inner  nuclear  layer,  however,  there  are  stellate  ganglion  cells  with 
neuraxons  which  pursue  a  horizontal  course  and  then  turn  inward  to  join 
the  optic  nerve  fibers,  as  shown  in  Fig.  454.  The  existence  of  such  fibers 
has  been  denied  by  some  writers.  The  neuraxons  of  other  stellate  gang- 
lion cells  in  this  region  end  in  relation  with  the  bases  of  the  visual  cells 
(Fig.  454,  +). 

Toward  the  inner  reticular  layer,  the  inner  nuclear  layer  contains 
the  bodies  of  ganglion  cells,  which  appear  to  lack  a  chief  or  large  process, 
and  are  therefore  called  "amakrine"  cells.  They  send  branching  fibers 
into  the  inner  reticular  layer,  where  they  interlace  with  the  fine  varicose 
branches  of  the  bipolar  cells,  and  with  the  ramifications  of  the  dendrites 
from  the  ganglion  nervi  optici. 

lie  ganglion  cell  layer  consists  of  a  single  row  of  large  multipolar 
cells  containing  Nissl's  bodies.  Certain  of  these  cells  because  of  excep- 
tional size  are  known  as  "  giant  ganglion  cells,"  and  they  occur  at  quite 
regular  intervals.  "Twin  cells"  have  been  found,  consisting  of  two  cell 
bodies  united  by  a  sjiort  bridge;  only  one  of  the  pair  has  a  neuraxon. 

The  nerve  fiber  layer  consists  chiefly  of  the  non-medullated  neuraxons 
of  the  ganglion  cells,  arranged  in  plexiform  bundles.  Occasionally  the 
neuraxons  send  collaterals  back  to  the  ganglion  cell  layer,  where  they 
branch  about  the  cell  bodies  (Fig.  454).  The  fiber  layer  contains  also 
neuraxons  which  have  come  out  from  the  brain  to  terminate  in  free 
branches  among  the  cells  of  the  inner  nuclear  layer. 


EYE 


447 


In  addition  to  the  nervous  elements,  the  retina  contains  blood  vessels 
and  a  supporting  framework  of  neuroglia  cells.  The  largest  vessels  are 
toward  the  fiber  layer  (Fig.  453),  in  thich  they  travel  to  and  from  the  cen- 
tral vessels  in  the  papilla.  The  neuroglia  framework  consists  chiefly  of 
radial  (or  Miiller's)  fibers,  which  are  elongated  cells  extending  from  the 
internal  to  the  external  limiting  membrane.  Beyond  this  membrane  they 
send  short  processes  between  the  rods  and  cones,  forming  "  fiber  baskets " 
(Fig.  455).  The  radial  fibers  are  not  isolated  cells  but  are  parts  of  a 
general  syncytium,  being  connected  by  a  network  of  processes  which  pene- 
trate all  the  layers  of  the  retina  (Fig.  454).  The  external  limiting  mem- 
brane, through  which  the  rods  and  cones  pass,  is  formed  by  the  coa- 


: 


Fiber  basket. 


__  Nucleated  part  of  the 


^^»  Basal  pyramid. 


-*  Precipitate. 


FIG.  455.— GOLGI  PREPARATION  OF  RADIAL  FIBERS  IN  A  THICK  SECTION  OF  THE  HUMAN  RETINA. 
The  fine  processes  of  the  fibers  in  the  outer  nuclear  layer  appear  as  a  compact  mass.      X   360. 

lescence  of  these  processes,  and  the  internal  limiting  membrane  is  made  up 
of  the  closely  adjacent  basal  expansions  of  the  radial  fibers.  The  nuclei 
of  the  fibers  are  found  in  the  inner  nuclear  layer.  In  additiod  to  the  radial 
fibers  there  are  neuroglia  cells  with  horizontal  or  tangential  branches 
(Fig.  454,  "oo")«  As  in  the  central  nervous  system,  some  of  the  stellate 
groups  of  fibers  do  not  contain  nuclei. 

Two  modifications  of  the  retina  require  special  description,  namely, 
the  fovea  centralis,  which  is  the  region  of  most  acute  vision,  and  the  pars 
ciliaris,  which  is  the  rudimentary  peripheral  portion. 

Macula  lutea  and  fovea  centralis.  When  vision  is  centered  upon  a 
particular  object,  the  eyes  are  so  directed  that  the  image  of  the  object  falls 
upon  the  macula  lutea,  or  yellow  spot  of  the  retina,  within  which  there  is 
a  depression,  the  fovea  centralis.  The  macula  sends  straight  slender 


448 


HISTOLOGY 


h5         H 


EYE 


449 


fibers  to  the  papilla  of  the  optic  nerve,  which  is  close  by  on  its  median 
side;  other  coarser  optic  fibers  diverge  as  they  pass  the  macula,  forming 
an  ellipse  around  it.  The  retinal  layers  of  the  macula  are  arranged  as 
shown  in  Fig.  456.  At  its  border  the  number  of  rod  cells  diminishes,  and 
within  the  macula  they  are  entirely  absent.  The  nuclei  of  the  numerous 
cone  cells,  which  are  here  somewhat  smaller  than  elsewhere,  form  an  inner 
nuclear  layer  of  twice  the  usual  thickness.  The  basal  portions  of  the 
cone  cells  make  a  broad  Henle's  fiber  layer,  and  slope  away  from  the 
fovea.  The  bipolar  cells  of  the  ganglion  retinae  are  so  numerous  that 
their  nuclei  may  form  nine  rows.  The  ganglion  cells  of  the  optic  nerve 
are  also  abundant.  All  of  these  strata  become  thin  toward  the  fovea,  the 
deepest  part  of  which  contains  scarcely  more  than  the  cone  cells.  In 
some  individuals  the  slope  of  the  sides  of  the  fovea  is  less  steep  than  in  the 
figure;  its  depth  is  variable.  The  macula  and  fovea  are  saturated  with  a 
yellow  pigment  soluble  in  alcohol. 

Pars  ciliaris  retina.  The  optic  nerve  fibers  and  their  ganglion  cells 
disappear  before  reaching  the  ora  serrata.  The  cone  cells  extend  further 
toward  the  ora  than  the  rods,  but  the  last  of  them  appear  to  lack  outer 
segments.  By  the  thinning  of  the  reticular  layer,  the  nuclear  layers 
become  confluent  (Fig.  457).  Near  the  ora  serrata  large  clear  spaces 
normally  occur  in  the  outer  nuclear  layer,  and  they  may  extend  into  the 
deeper  layers  (Fig.  457).  The  radial  sustentacular  cells  form  a  simple 
columnar  epithelium  as  the  other  layers  disappear,  and  they  constitute 
the  visual  layer  of  the  pars  ciliaris.  The  pigmented  epithelium  is  appar- 
ently unmodified  as  it  extends  from  the  optic  to  the  ciliary  portion.  Along 
the  inner  surface  of  the  ciliary  part  of  the  retina,  the  cells  of  the  visual 
layer  produce  closely  packed  horizontal  fibers,  which  form  a  refractive 
hyaline  membrane. 

Zonula  ciliaris.  Some  of  the  fine  homogeneous  fibers  arising  from  the 
pars  ciliaris  immediately  in  front  of  the  ora  serrata  enter  the  vitreous  body, 
but  a  much  larger  number  pass  between  the  ciliary  processes  to  the  lens. 
They  are  attached  to  the  borders  of  its  capsule,  overlapping  slightly  its 
anterior  and  posterior  surfaces.  Thus  they  form  the  zonula  ciliaris  (sus- 
pensory ligament)  which  holds  the  lens  in  place  (Fig.  452).  The  zonula 
is  not  a  continuous  layer,  nor  does  it  consist  of  two  laminae,  one  to  the  an- 
terior and  the  other  to  the  posterior  surface  of  the  lens,  with  a  space  be- 
tween them.  It  consists  rather  of  numerous  bundles,  between  which  and 
the  vitreous  body,  and  among  the  bundles  themselves,  there  are  zonular 
spaces  (canals  of  Petit)  which  communicate  with  the  posterior  chamber. 

OPTIC  NERVE. 

In  its  intraorbital  portion  the  optic  nerve  is  surrounded  by  prolonga- 
tions of  the  meninges.     On  the  outside  is  the  dural  sheath,  consisting  of 
29 


45° 


HISTOLOGY 


^c^3 

*o  2      G 

U.-9     * 


I  1 1!  I 


i 


J.U "  Vacuole." 


Radial  fibers  of 
Muller. 


Pars  ciliaris  retinae. 


EYE 


451 


dense  connective  tissue  with  many  elastic  fibers.  The  outer  connective 
tissue  bundles  tend  to  be  longitudinal  and  the  inner  circular.  Internally 
the  outer  sheath  is  connected  with  the  arachnoid  layer  by  a  few  dense 
strands  of  tissue,  and  the  arachnoid  joins  the  pial  sheath  by  many  branched 
trabeculae.  The  pia  surrounds  the  entire  nerve  and  sends  anastomosing 
septa  among  the  bundles  of  nerve  fibers.  The  latter  are  slender  and 
medullated,  but  without  a  neurolemma;  they  are  supported  by  long- 
rayed  neuroglia  cells,  which  are  found  between  the  individual  fibers,  but 
are  most  numerous  at  the  periphery  of  the  bundles  and  around  the  entire 
nerve.  Thus  the  optic  nerve  differs  from  the  peripheral  nerves,  and 
resembles  a  cerebral  commissure. 

At  the  posterior  surface  of  the  eye-ball  (or  bulbus  oculi),  the  dura 
blends  with  the  sclera.  Continuous  with  both  is  the  dense  elastic  lamina 
cribrosa  which  is  perforated  by  the  optic  nerve  fibers.  The  chorioid  and 
the  pia  are  also  in  relation  with  this  lamina  (Fig.  458).  As  the  optic 


Central  artery. 
Fibers  of  the  lamina  cribrosa.  Central  vein. 


Hyaloid  membrane 
loosened. 


Bundles  of  the  optic  nerve.  =_ 
Pial  sheath.   - 

Arachnoidal  sheath. 
Dural  sheath. 


FIG.  458. — LONGITUDINAL  SECTION  OF  THE  OPTIC  ENTRANCE  OF  A  HUMAN  EYE.     X   15. 

Above  the  lamina  cribrosa  is  seen  the  narrowing  of  the  optic  nerve,  due  to  its  loss  of  myelin.  The  central 
artery  and  vein  have  been  for  the  most  part  cut  longitudinally,  but  above  at  several  points  trans- 
versely. 

nerve  penetrates  the  lamina,  its  fibers  lose  their  myelin  and  radiate  into 
the  nerve  fiber  layer  of  the  retina.  The  central  artery  and  vein  of  the 
retina  enter  the  optic  nerve  in  its  distal  half,  and  appear  at  the  fundus  of 
the  eye  in  the  center  of  the  optic  papilla.  Their  branches  spread  in  the 
inner  layers  of  the  retina,  which  are  covered  by  the  membrana  limitans 
interna  (Fig.  453). 

LENS. 

The  lens  is  a  biconvex  structure  having  an  anterior  and  a  posterior 
pole,  and  a  vertical  equatorial  plane.     It  is  enclosed  in  a  thick  transparent 


452 


HISTOLOGY 


elastic  capsule,  6.5-25  /*  thick  in  front  and  2-7  n  thick  behind,  which  is 
apparently  derived  from  the  lens  itself.  Within  the  capsule  the  anterior 
surface  of  the  lens  is  formed  by  the  lens  epithelium,  a  single  layer  of  cells 
2.5  M  thick  at  the  pole,  but  becoming  taller  toward  the  equator.  There 
they  are  continuous  with  the  elongated  lens  fibers  of  the  posterior  layer, 
which  collectively  are  called  the  substantia  lentis. 

Originally  the  fibers  multiply  throughout  the  lens,  but  in  later  stages 
the  formation  of  new  fibers,  as  indicated  by  the  presence  of  mitotic  figures, 
is  limited  to  the  region  of  transition  between  the  lens  epithelium  and 
the  mass  of  lens  fibers  (Figs.  451,  E,  and  460).  When  first  formed  the 
fibers  are  short,  but  they  increase  in  length  and  become  six-sided  prisms, 
somewhat  enlarged  at  one  or  both  ends.  The  first  fibers  extend  from  one 
surface  of  the  lens  to  the  other.  Later  these  become  buried  in  by  the  new 


C 


FIG.  459. — LENS  FIBERS  OF  A  NEW-BORN  INFANT. 

A,  Isolated  lens  fibers;  three  with  smooth  and  one 
with  dentate  borders.  X  240.  B,  Human 
lens  fibers  cut  transversely;  c,  section 
through  club-shaped  ends.  X  560. 


FIG.  460. — CAPSULE  AND  EPITHELIUM  OF  A  LENS  OF 
ADULT  MAN. 

C,  Tangential  section.  D.  Meridional  section  across 
the  equator  of  the  lens;  i,  capsule;  2,  epithelium; 
3,  lens  fibers.  X  240. 


fibers  formed  at  the  periphery,  and  thus  they  constitute  the  nucelus  of  the 
lens.  This  is  a  dense  mass  of  somewhat  shrunken  fibers,  which  have  lost 
their  nuclei  and  have  acquired  wavy  or  notched  margins  (Fig.  459)- 
The  outer  fibers  of  the  cortical  substance  are  softer.  They  have  smooth 
borders,  and  nuclei  which  are  chiefly  in  the  equatorial  plane.  Their  proto- 
plasm is  transformed  into  a  clear  fluid  substance,  said  to  be  chiefly  a 
globulin.  The  fibers  are  united  to  one  another  by  a  small  amount  of 
cement  substance,  which  is  more  abundant  at  the  poles,  at  each  of  which  it 
forms  a  "lens  star,"  usually  with  nine  rays. 

When  the  fibers  formed  at  the  periphery  of  the  original  nucleus  elongate  so  as  to 
cover  it  in,  they  do  not  extend  from  one  pole  to  the  other.  Those  that  reach  the  ante- 
rior pole  fall  short  of  the  posterior  pole,  terminating  along  a  horizontal  suture  of 
cement  substance;  and  conversely  those  that  reach  the  posterior  pole  terminate 
anteriorly  along  a  linear  vertical  suture.  As  the  lens  becomes  larger,  the  linear  sutures 
at  either  pole  are  replaced  by  tri-radiate  or  Y-shaped  stars,  one  of  which  is  inverted. 


EVE  453 

Lens  fibers  starting  near  the  center  of  one  star  end  near  the  tips  of  the  rays  of  the 
other,  and  vice  versa.  When  the  stars  become  nine-rayed  the  arrangement  of  the 
fibers  is  very  intricate.  Without  crossing  one  another,  and  without  any  of  them  being 
long  enough  to  pass  from  pole  to  pole,  they  cover  the  lens  with  even  layers.  The 
development  of  the  stars  is  described  by  Rabl  (Ueber  den  Bau  und  Entwicklung  der 
Linse,  Leipzig,  1900).  As  a  result  of  its  structure  the  lens  may  be  separated  into  con- 
centric lamellae,  but  Rabl  considers  that  the  meridional  segments,  or  "radial  lamellae," 
of  which  the  lens  contains  about  two  thousand,  are  its  essential  subdivisions. 

VITREOUS  BODY. 

The  corpus  vitreum  consists  of  the  fluid  vitreous  humor,  together  with 
looser  or  denser  strands  of  fibrous  stroma  which  stretch  across  it  in  all 
directions.  Although  it  is  difficult  to  recognize  any  definite  arrangement 
in  the  stroma,  certain  pathological  cases  suggest  that  it  is  distributed  like 
the  septa  of  an  orange.  The  cells  of  the  vitreous  body  are  round  forms, 
probably  leucocytes,  and  stellate  or  spindle-shaped  connective  tissue 
cells,  sometimes  degenerating  and  vacuolated,  which  invaded  the  vitreous 
body  with  the  blood  vessels.  The  latter  have  atrophied  and  been  resorbed, 
except  for  occasional  shreds  and  filaments.  Such  opacities,  which  occur 
normally,  are  observed  when  looking  at  a  bright  light,  and  are  frequently 
troublesome  to  those  beginning  to  use  the  microscope;  because  of  their 
erratic  motion  they  are  known  to  physiologists  as  musccs  volitantes.  In 
old  age,  in  eyes  otherwise  normal,  crystals  may  form  in  the  vitreous 
humor  and  float  about,  "falling  like  a  shower  to  the  bottom  of  the  eye  when 
the  eye  is  held  still."  Surrounding  the  vitreous  body  there  is  a  very  re- 
sistant thick  fibrous  layer,  which  is  continuous  anteriorly  with  the  hyaloid 
membrane  of  the  ciliary  part  of  the  retina. 

TUNICA  VASCULOSA. 

Chorioid.  Between  the  sclera  and  the  chorioid  there  is  a  loose  tissue 
containing  many  elastic  fibers  and  branched  pigment  cells,  together  with 
flat  non-pigmented  cells.  In  separating  the  sclera  from  the  chorioid,  this 
layer  is  divided  into  the  lamina  fusca  of  the  sclera  and  the  lamina  supra- 
chorioidea.  Internal  to  the  latter  is  the  lamina  vasculosa,  which  forms  the 
greater  part  of  the  chorioid.  It  contains  many  large  blood  vessels  im- 
bedded in  a  loose  elastic  connective  tissue;  some  of  its  cells  being  branched 
and  pigmented;  others  without  pigment  are  flat  and  arranged  in  layers  sur- 
rounding the  vessels.  A  thin  inner  layer  of  blood  vessels,  the  lamina  chorio- 
capillaris,  consists  of  a  very  close  network  of  wide  capillaries.  The  chorio- 
capillaris  is  separated  from  the  pigmented  epithelium  of  the  retina  by  a 
structureless  elastic  lamella  which  may  be  2  n  thick.  This  lamina  basalis 
shows  the  imprint  of  the  polygonal  retinal  cells  on  its  inner  surface,  and  is 
associated  with  fine  elastic  networks  toward  the  choriocapillaris. 


454 


HISTOLOGY 


Between  the  vascular  lamina  and  the  choriocapillaris,  there  is  a  boundary  layer 
consisting  of  a  fine  elastic  network,  generally  without  pigment.  Here  in  ruminants 
and  horses  there  are  many  wavy  bundles  of  connective  tissue,  which  give  to  the  eyes 
of  those  animals  a  metallic  luster.  Such  a  layer  is  known  as  the  tapetum  fibrosum. 
The  similarly  iridescent  tapetum  cellulosum  of  the  carnivora  is  formed  of  several 
layers  of  flat  cells  which  contain  numerous  fine  crystals. 

The  ciliary  body  encircles  the  eye  as  a  muscular  band,  attached  to  the 
inner  surface  of  which  there  are  from  70  to  80  meridional  folds,  the  ciliary 
processes  (Fig.  452).  The  equator  of  the  eye  is  vertical,  like  that  of  the 
lens,  and  the  meridians  are  antero-posterior.  The  processes  begin  low  at 
the  ora  serrata  and  rise  gradually  to  a  height  of  i  mm.,  terminating 
abruptly  near  the  border  of  the  lens.  Each  process  consists  of  fibrillar 
connective  tissue  containing  numerous  elastic  fibers  and  blood  vessels, 
and  is  bounded  toward  the  pars  ciliaris  retinae  by  a  continuation  of  the 


Cross  and  longitudinal 
sections  of  bundles 
of  scleral  fibers. 

Lamina  supra- 
chorioidea. 


Lamina  vasculosa. 


'. Boundary  zone. 

—  Choriocapillaris. 
5^       Basal  membrane. 


-^  Pigment  layer  of  the 

retina. 

FIG.  461. — VERTICAL  SECTION  THROUGH  A  PART  OF  THE  HUMAN  SCLERA  AND  THE  ENTIRE  THICKNESS  OF 

THE  CHORIOID.     X   100. 

g,  Large  vessels;  p,  pigment  cells;  c,  cross  section  of  capillaries. 

lamina  basalis,  which  is  thrown  into  intersecting  folds.  The  ciliary  proc- 
esses, which  are  compressible,  may  serve  to  prevent  the  increase  of  intra- 
ocular pressure  during  the  contraction  of  the  ciliary  muscle;  and  the 
fluid  within  the  eye  is  derived  from  the  vessels  which  they  contain.  The 
ciliary  muscle  is  a  band  of  smooth  muscle  fibers  about  3  mm.  broad  and 
0.8  mm.  thick  anteriorly;  it  arises  beneath  the  sinus  venosus  of  the  sclera 
and  tapers  toward  the  ora  serrata  (Fig.  425).  It  consists  of  three  sets 
of  fibers,  the  meridional,  radial,  and  circular.  The  meridional  fibers  (Fig. 
45  2,  p.  443)  are  next  to  the  sclera,  grouped  in  numerous  bundles  with  elastic 
tissue  intermingled.  They  extend  to  the  smooth  part  of  the  chorioid, 
and  constitute  the  tensor  chorioidece.  The  radial  fibers  are  directed  to- 


EVE 


455 


ward  the  center  of  the  eye-ball.  They  form  a  middle  layer  of  curving 
fibers  which  blend  with  the  meridional  fibers  externally.  The  circular 
fibers,  which  vary  in  number  in  different  individuals,  form  that  part  of  the 
ciliary  muscle  which  is  nearest  to  the  equator  of  the  lens.  The  contrac- 
tion of  these  muscles  affects 
the  shape  of  the  lens,  which  is 
attached  to  the  adjacent  tissue 
by  the  zonula. 

The  iris  consists  of  its  stroma 
anteriorly,  and  the  pars  iridica 
retina  posteriorly,  and  is  covered 
by  the  mesenchymal  epithelium 
of  the  chambers  of  the  eye. 
The  anterior  epithelium  is  a 
simple  layer  of  flat  polygonal 
cells  (sometimes  called  "endo- 
thelium").  It  rests  upon  a 
loose  network  of  stellate  cells, 
in  part  pigmented,  resembling 
the  reticulum  of  a  lymph  gland.  This  is  followed  by  the  loose  connec- 
tive tissue  of  the  stroma,  likewise  containing  networks  of  stellate  cells, 
which  in  blue  eyes  are  not  pigmented.  The  very  few  elastic  fibers  are 
limited  to  the  posterior  layers,  where  they  are  radially  arranged  in  rela- 


Mesenchymal 
epithelium. 


Loose  connective 
tissue. 


FIG.  462. — A,  FROM  A  TEASED  PREPARATION  OF  A  HUMAN 
CHORIOID.  X  240.  p,  Pigment  cells;  e,  elastic  fibers; 
k,  nucleus  of  a  flat  non-pigment ed  cell;  the  cell  body 
is  invisible. 

B,  PORTION  OF  A  HUMAN  CHORIOCAPILLARIS  AND  THE 
ADHERENT  LAMINA  BASALIS.  X  240.  c,  Wide 
capillaries,  some  of  which  contain  (b)  blood-corpus- 
cles; e,  lamina  basalis,  showing  a  fine  "lattice  work." 


Vascular  layer. 


Spindle  cell  layer. 


FIG.  463. — VERTICAL  SECTION  OF  THE  PUPILLARY  PORTION  OF  A  HUMAN  IRIS.     X  100.     About  one-fifth 

of  the  entire  width  of  the  iris  is  shown. 

g,  Blood  vessel,  with  thick  connective  tissue  sheath;    m,  sphincter  pupillae  muscle  cut  transversely;    r» 

pupillary  border  of  the  iris. 

tion  to  the  pupil.  The  stroma  contains  numerous  radial  blood  ves- 
sels with  thick  connective  tissue  coats,  but  (in  man)  without  muscu- 
lature or  elastic  fibers.  In  the  vascular  layer,  toward  the  pupillary 
border  of  the  iris,  there  is  a  band  of  circular  smooth  muscle  fibers,  i 
mm.  deep;  this  is  the  sphincter  pupillce.  It  is  invested  with  many 


456 


HISTOLOGY 


prolongations  of  the  stromatic  network,  the  polygonal  meshes  of  which 
are  radially  elongated.  .  The  dilatator  pupillce  is  a  peculiar  membrane 
of  smooth  muscle  fibers  on  the  posterior  surface  of  the  vascular 
layer,  stretching  from  the  connective  tissue  between  the  muscle 
bundles  of  the  sphincter,  to  that  between  the  ciliary  muscles.  Its  fibers 
consist  of  an  anterior  contractile  portion,  and  a  posterior  nucleated  and 
pigmented  portion.  The  anterior  parts  form  a  continuous  layer,  readily 
seen  in  radial  sections  as  "Henle's  spindle  cell  layer/'  which  is  a  clear 
non-nucleated  stripe,  2-5  /*  wide  (Fig.  463).  The  nucleated  portions  of 
the  fibers  appear  to  blend  with  the  pigmented  retinal  layer  of  the  iris, 
from  which  they  are  derived.  These  muscles  are  therefore  ectodermal. 

The  two  layers  of  the  optic  cup  are  intimately  blended  in  the  thin 
stratum  which  forms  the  posterior  layer  of  the  iris.  Except  in  albinos, 
this  pars  iridica  retinae  is  deeply  pigmented.  Posteriorly  it  is  covered 
by  a  continuation  of  the  hyaline  membrane  of  the  pars  ciliaris. 

TUNICA  FIBROSA. 

The  sclera,  toward  the  chorioid,  is  bounded  by  the  pigmented  lamina 
fusca.  This  is  "a  loose  tissue  containing  branched  pigment  cells  and 
flattened  connective  tissue  cells.  Except  for  this  boundary  layer,  the 
sclera  consists  of  densely  interwoven  bundles  of  connective  tissue,  chiefly 
meridional  and  longitudinal.  Elastic  fibers  accompany  the  bundles,  and 
are  especially  abundant  at  the  insertions  of  the  ocular  muscles.  The  flat 
irregular  cells  of  the  connective  tissue  are  surrounded  by  tissue  spaces  as 
in  the  cornea,  and  anteriorly  the  cornea  and  sclera  are  continuous  with  one 
another.  The  transition,  however,  is  quite  abrupt  and  the  boundary  is 
oblique,  so  that  the  rim  of  the  cornea  is  bevelled  at  the  expense  of  its  an- 
terior surface. 

The  cornea  (Fig.  464)  consists  of  an  outer  epithelium,  external  basal 
membrane,  substantia  propria,  internal  basal  membrane,  and  mesen- 
chymal  epithelium  bounding  the  anterior  chamber.  The  corneal  epithe- 
lium, about  0.03  mm.  thick,  is  stratified  and  consists  of  a  basal  layer  of 
clearly  outlined  columnar  cells  followed  by  three  or  four  rows  of  cuboidal 
cells  and  several  layers  of  flattened  superficial  cells.  The  outer  cells 
retain  their  nuclei.  Peripherally  the  epithelium  is  continuous  with  that 
of  the  conjunctiva  bulbi.  The  anterior  basal  membrane  (Bowman's)  is 
an  almost  homogeneous  layer,  sometimes  as  much  as  o.oi  mm.  thick. 
Superficially  it  connects  with  the  epithelial  cells  by  spines  and  ridges. 
Beneath,  it  blends  with  the  substantia  propria,  of  which  it  is  a  modification. 
Since  it  is  not  formed  of  elastic  substance  the  name  "  anterior  elastic  mem- 
brane" is  not  justified. 

The  substantia  propria  consists  of  fine  straight  fibrils  of  connective 


EYE 


457 


tissue,  bound  together  in  bundles  of  almost  uniform  thickness  by  an 
interfibrillar  substance,  perhaps  fluid;  these  bundles  are  joined  to  one 
another  by  an  interfascicular  cement,  so  that  they  form  a  succession  of 


Epithelium. 
Anterior  basal  membrane. 


Substantia  propria. 


Posterior  basal  membrane. 


Mesenchymal  epithelium. 

FIG.  464. — VERTICAL  SECTION  OF  A  HUMAN  CORNEA.     X  100. 


Corneal  canaliculus.        Corneal  space. 
FIG.  465. — CORNEAL  SPACES  AND  CANALICULI  (IN 
WHITE)  FROM   A    HORIZONTAL    SECTION    OF 
THE  CORNEA  OF  AN  Ox.     Silver  preparation. 
X  240. 


Corneal  cells. 

FIG.  466. — CORNEAL  CELLS  FROM  A  HORIZONTAL 
SECTION  OF  THE  CORNEA  OF  A  RABBIT.     X  240. 


superposed  flat  lamellae,  parallel  with  the  corneal  surface.  Oblique  bun- 
dles, the  so-called  arcuate  fibers,  are  found  especially  in  the  anterior 
layers,  where  they  pass  from  one  lamella  to  that  next  above  or  below. 


458  HISTOLOGY 

Numerous  tense  elastic  fibers  are  found  especially  in  the  deeper  layers, 
where  they  form  a  fine  network  over  the  posterior  elastic  membrane. 

Within  the  cement  substance,  there  is  a  system  of  branched  canaliculi, 
dilated  in  places  to  form  oval  spaces.  The  latter  are  between  the  lamellae, 
but  the  canaliculi  extend  also  among  the  constituent  fiber-bundles. 
Within  the  spaces,  there  are  flat  stellate  anastomosing  cells  or  "corneal 
corpuscles/'  the  branches  of  which  extend  into  the  canals  and  tend  to 
unite  with  those  of  neighboring  cells,  at  right  angles  (Fig.  466).  The  cells 
and  their  processes  are  more  or  less  surrounded  by  serous  fluid.  Leuco- 
cytes enter  the  canals,  and  are  normally  found  in  the  cornea;  if  the 'cornea 
is  inflamed  they  become  abundant.  Blood  vessels  and  lymphatic  vessels 
are  absent. 

The  posterior  basal  or  elastic  membrane  (Descemet's  membrane)  is  a 
structure  clear  as  glass,  6  ju  thick.  Its  posterior  surface  is  covered  by  a 
simple  layer  of  flat  polygonal  cells  (Fig.  464),  which  form  a  part  of  the 
lining  of  the  anterior  chamber.  Toward  the  periphery  of  the  cornea  in 
adults,  the  posterior  surface  of  the  elastic  membrane  presents  rounded 
elevations,  and  the  posterior  epithelium  becomes  continuous  with  the 
anterior  epithelium  of  the  iris  (Fig.  452).  In  this  " angle,"  the  cornea 
receives  connective  tissue  prolongations  from  the  iris,  which  form  the 
pectinate  ligament  of  the  iris — a  structure  highly  developed  in  the  horse 
and  cow,  but  rudimentary  in  man. 

BLOOD  VESSELS. 

The  central  vessels  of  the  retina  supply  a  part  of  the  optic  nerve,  and 
the  retina;  the  ciliary  vessels  supply  the  rest  of  the  eye.  These  two  sets 
of  vessels  anastomose  with  one  another  only  at  the  entrance  of  the  optic 
nerve  (Fig.  467). 

The  ciliary  arteries  include  (i)  the  short  posterior  ciliary  arteries;  (2) 
the  long  posterior  ciliary  arteries;  and  (3)  the  anterior  ciliary  arteries.  The 
three  groups  will  be  considered  in  turn. 

1.  After  supplying  the  posterior  half  of  the  surface  of  the  sclera,  some  twenty 
branches  of  the  short  posterior  ciliary  arteries  penetrate  the  sclera  around  the  optic 
nerve.     They  form  the  capillaries  of  the  lamina  choriocapillaris.     At  the  entrance  of 
the  optic  nerve  they  anastomose  with  branches  of  the  central  artery  of  the  retina  (c) 
and  thus  form  the  circulus  arteriosus  nervi  optici.     At  the  ora  serrata  they  anastomose 
with  recurrent  branches  of  the  long  posterior  ciliary  and  the  anterior  ciliary  arteries. 

2.  The  two  long  posterior  ciliary  arteries  also  penetrate  the  sclera  near  the  optic 
nerve  (Fig,  467,  i).     They  pass,  one  on  the  nasal  and  the  other  on  the  temporal  side 
of  the  eye,  between  the  chorioid  and  sclera  to  the  ciliary  body.     There  each  artery 
divides  into  two  branches  which  follow  the  ciliary  border  of  the  iris,  and  connect  with 
the  corresponding  branches  from  the  artery  of  the  opposite  side,  thus  encircling  the 
iris  with  an  arterial  ring.     This  is  the  circulus  iridis  major  (Fig.  467,  2),  from  which 


EYE 


459 


numerous  branches  extend  to  the  ciliary  processes  (3)  and  to  the  iris  (4).  Near  the 
pupillary  border  of  the  iris,  the  arteries  form  an  incomplete  ring,  the  circulus  iridis 
minor. 

3.  The  anterior  ciliary  arteries  proceed  from  those  supplying  the  recti  muscles, 
penetrate  the  sclera  near  the  cornea,  and  in  part  join  the  circulus  iridis  major,  in  part 
supply  the  ciliary  muscle,  and  in  part  through  recurrent  branches,  connect  with  the 

Branches  Branches 

to  the      to  the 
Sinus     corneal  conjunctiva 
venosus  border,      bulbi. 
sclerae.     ^-^  V       ^-—    Connection  with  the  lamina  choriocapillaris. 


Cornea. 


Vena"1  1  ciliaris  anterior. 


Venous  ]  episcleral 

I  branches  of  the 
[anterior 

Arterial  j  ciliary  vessels. 


Capillaries  of  the  lamina  choriocapillaris. , 

c 


Vena  vorticosa. 


Venous  \  episcleral  branches 
Arterial         /  of  the  short  posterio 
ciliary  vessels. 

-1 

Ye°a  .    )  ciliaris  posterioris  brevis. 

/\rt  ens.  j 


Outer) 

y  vessels  of  the  sheath. 
Inner  .  . .  .  ) 


Short  posterior  ciliary  arteries. 


Vena  Arteria 
centralis  retinae. 


FIG.  467. — BLOOD  VESSELS  OF  THE  EYE.     (After  Leber.) 

The  retina,  optic  nerve  and  tunica  fibrosa  are  stippled;  the  tunica  vasculosa  is  blank.     V,  Connection  of 
the  anterior  ciliary  artery  with  the  circulus  iridis  major  (2). 


lamina  choriocapillaris.  Before  penetrating  the  sclera,  the  anterior  ciliary  arteries 
give  off  posterior  branches  for  the  anterior  half  of  the  sclera,  and  anterior  branches  for 
the  conjunctiva  bulbi  and  the  corneal  border.  The  cornea  itself  is  without  vessels, 
but  at  its  border,  between  the  anterior  lamellae  of  the  substantia  propria,  there  are 
terminal  loops. 


460  HISTOLOGY 

The  veins  generally  proceed  toward  the  equator,  uniting  in  four  (less 
often  in  5  or  6)  vena  vorticosce.  These  pass  directly  through  the  sclera 
and  empty  into  one  of  the  ophthalmic  veins.  Besides  the  venae  vorticosae 
there  are  small  veins  accompanying  the  short  posterior  and  the  anterior 
ciliary  arteries.  The  short  ciliary  veins  receive  branches  from  the  ciliary 
muscle,  the  episcleral  vessels,  the  conjunctiva  bulbi  and  the  periphery  of 
the  cornea.  The  episcleral  veins  also  connect  with  the  venae  vorticosae. 
Within  the  sclera,  near  the  cornea,  there  is  a  circular  vein, receiving  small 
branches  from  the  capillaries  of  the  ciliary  muscle.  This  sinus  venosus 
sclercR  (canal  of  Schlemm)  connects  with  the  anterior  ciliary  veins. 

Arteria  centralis  retina.  The  central  artery  of  the  retina  enters  the 
optic  nerve  15-20  mm.  from  the  eye-ball,  passes  to  its  center  and  proceeds 
to  the  optic  papilla.  There  it  divides  into  two  branches  directed  upward 
and  downward  respectively,  and  these  by  further  subdivision  supply  the 
entire  pars  optica  retinae.  Within  the  optic  nerve  the  artery  sends  out 
numerous  little  branches  which  anastomose  with  small  vessels  that  have 
entered  the  sheaths  from  the  surrounding  fat;  and  also  with  branches  of 
the  short  posterior  ciliary  arteries  (Fig.  467,  £>). 

The  central  vein  of  the  retina  receives  two  main  branches  at  the  optic 
papilla  and  follows  the  artery  along  the  axis  of  the  optic  nerve. 

CHAMBERS  AND  TISSUE  SPACES  OF  THE  EYE. 

The  eye  contains  no  lymphatic  vessels,  but  is  provided  with  communi- 
cating tissue  spaces,  bounded  by  loose  cells  or  mesenchymal  epithelia. 
They  include  the  corneal  and  scleral  canaliculi,  and  the  anterior  and  poste- 
rior chambers;  the  latter  connect  with  one  another  through  the  capillary  in- 
terval between  the  lens  and  iris.  The  posterior  chamber  extends  into  the 
zonular  spaces;  and  there  are  irregular  extensions  of  the  anterior  chamber, 
associated  with  the  pectinate  ligament  of  the  iris,  called  spaces  of  the  angle 
of  the  iris  (spaces  of  Fontana).  The  latter  are  but  slightly  developed  in 
man.  Posteriorly  the  tissue  spaces  include  the  hyaloid  canal  of  the 
vitreous  body;  the  very  narrow  perichorioideal  space  between  the  chorioid 
and  sclera;  the  subdural  and  arachnoid  spaces  of  the  optic  sheaths, 
named  the  intravaginal  spaces;  and  finally  the  interfascial  space  (of  Tenon) 
which  surrounds  most  of  the  sclera  and  is  prolonged  as  a  supradural  space 
around  the  optic  nerve.  These  spaces  may  be  filled  from  the  arachnoid 
space  about  the  brain.  They  contain  a  "filtrate  from  the  vessels."  The 
interfascial  and  perichorioideal  spaces  hold  but  little  fluid;  acting  as 
bursae,  they  facilitate  the  movements  of  the  eye. 

NERVES. 

Apart  from  the  optic  nerve,  the  eye  is  supplied  by  the  short  ciliary 
nerves  from  the  ciliary  ganglion,  and  the  long  ciliary  nerves  from  the  naso- 


EYE 


461 


Epithelium 

Anterior 

basal 
membrane. . . 


ciliary  branch  of  the  ophthalmic  nerve.  The  ciliary  nerves  penetrate  the 
sclera  near  the  optic  nerve  and  send  branches  containing  ganglion  cells 
to  the  vessels  of  the  chorioid.  The  main  stems  pass  forward  between  the 
chorioid  and  sclera  to  the  ciliary  body,  where  they  form  a  circular  gang- 
lionated  plexus,  the  plexus  gangliosus  ciliaris.  Its  branches  extend  to 
the  ciliary  body,  the  iris  and  the  cornea,  and  are  described  as  follows: 

The  nerves  of  the  ciliary  body  form  a  delicate  network  on  its  scleral 
surface;  they  supply  its  muscle  fibers  and  those  of  the  vessels  with  slender 
motor  endings;  and  between  the 
ciliary  muscle  bundles  they  have 
branched  free  endings,  perhaps 
sensory. 

The  medullated  nerves  of  the 
iris  lose  their  myelin  and  form 
plexuses  as  they  pass  toward  the 
pupillary  margin.  A  sensory 
plexus  is  found  just  beneath  the 
anterior  surface,  and  motor  fibers 
supply  the  sphincter,  dilator  and 
vascular  muscles.  The  existence  of  ganglion  cells  in  the  human  iris 
is  denied. 

The  nerves  of  the  cornea  enter  it  from  the  plexus  annularis  in  the 
sclera  just  outside.  The  annular  plexus  also  sends  fibers  into  the  conjunc- 
tiva, where  they  end  in  networks,  and  in  bulbous  corpuscles  (Fig.  154, 
p.  1 60)  situated  in  the  connective  tissue  close  to  the  epithelium.  Such 
corpuscles  may  be  found  i  or  2  mm.  within  the  corneal  margin.  The 
corneal  nerves  become  non-medullated  and  form  plexuses  between  the 
lamellae  throughout  the  stroma.  They  extend  into  the  epithelium  and 
there  form  a  very  delicate  plexus  with  free  intercellular  endings. 


Substantia  <  — ==— _ 

propria. 
FIG.  468. — FROM  A  SECTION  OF  THE  HUMAN  CORNEA. 

X  240. 

n,  A  branching  nerve  penetrating  the  anterior  basal 
membrane;  s,  subepithelial  plexus  beneath  the 
cylindrical  cells;  a,  fibers  of  the  intraepithelial 
plexus  ascending  between  the  epithelial  cells. 


EYELIDS. 

The  eyelids  or  palpebra  (Fig.  469)  are  covered  with  thin  skin  pro- 
vided with  fine  lanugo  hairs;  small  sweat  glands  extend  into  the  corium, 
which  here  contains  pigmented  connective  tissue  cells.  The  subcutaneous 
tissue  is  very  loose,  having  many  elastic  fibers  and  few  or  no  fat  cells. 
Near  the  edge  of  the  lid  there  are  two  or  three  rows  of  large  hairs,  the 
eyelashes  or  cilia,  the  oblique  roots  of  which  extend  deep  into  the  corium. 
Since  they  are  shed  in  from  100  to  150  days  they  occur  in  various  stages  of 
development.  They  are  provided  with  small  sebaceous  glands,  and  the 
ciliary  glands  (of  Moll)  open  close  beside  or  into  their  sheaths.  The  ciliary 
glands  are  modified  sweat  glands,  with  simpler  coils,  which  may  show 
successive  constrictions;  " a  branching  of  the  tubules  has  been  observed." 


462  HISTOLOGY 

The  central  portion  of  the  eyelids  is  muscular.  Beneath  the  sub- 
cutaneous tissue  there  are  bundles  of  the  striated  orbicularis  palpebrarum 
extending  lengthwise  of  the  lid.  A  subdivision  of  this  muscle,  found  behind 
the  roots  of  the  cilia,  is  called  the  musculus  ciliaris  Riolani.  Posterior  to 
the  obicularis  muscle  are  found  the  terminal  radiations  of  the  tendon  of 
the  levator  palpebrce.  A  part  of  these  are  lost  in  connective  tissue;  another 
part,  associated  with  smooth  muscle  fibers,  are  inserted  into  the  upper 
border  of  the  tarsus  and  form  the  superior  tarsal  muscle.  This  occurs  in 
the  upper  lid,  but  correspondingly  in  the  lower  lid  the  radiations  from  the 
inferior  rectus  muscle  contain  smooth  muscle  fibers,  forming  the  inferior 
tarsal  muscle. 

The  inner  portion  of  the  lids  consists  of  the  conjunctival  epithelium 
and  the  underlying  connective  tissue,  including  the  tarsus.  This  is  a  plate 
of  dense  connective  tissue  which  gives  firmness  to  the  lid.  It  begins  at  the 
free  edges  and  extends  over  the  adjacent  two-thirds  of  the  lid,  close  to  the 
conjunctiva.  Imbedded  in  its  substance  in  either  lid,  there  are  about  30 
tarsal  (or  Meibomian)  glands,  which  open  along  the  palpebral  border. 
Each  of  them  consists  of  a  wide  excretory  duct,  surrounded  on  all  sides 
by  small  acini,  which  empty  into  the  duct  through  short  stalks.  In 
structure  they  resemble  sebaceous  glands.  At  the  upper  end  of  the 
tarsus  and  partly  enclosed  in  its  substance,  there  are  branched  tubular 
accessory  lachyrmal  glands.  They  occur  chiefly  in  the  medial  (nasal) 
half  of  the  lid. 

The  tunica  propria  of  the  palpebral  conjunctiva  contains  plasma  and 
lymphoid  cells;  the  latter  invade  the  epithelium,  beneath  which  in  some 
animals  they  form  nodules.  The  stratified  epithelium  of  the  skin  gradu- 
ally changes  to  that  of  the  conjunctiva,  which  has  several  basal  layers  of 
cuboidal  cells  and  a  superficial  layer  of  short  columnar  cells.  The  latter 
are  covered  by  a  thin  cuticula,  and  goblet  cells  are  found  among  them. 
The  transition  from  the  superficial  squamous  cells  to  the  columnar  form 
may  occur  at  the  posterior  edge  of  the  lid,  or  quite  high  on  the  conjunc- 
tival surface.  Toward  the  arch  where  the  palpebral  conjunctiva  becomes 
continuous  with  that  of  the  bulb,  the  epithelium  is  so  folded  that  in  sec- 
tions it  may  seem  to  form  glands. 

The  conjunctiva  bulbi  is  similar  to  that  of  the  lid.  Its  outer  epithe- 
lial cells,  however,  become  squamous  toward  the  cornea  and  over  the 
exposed  portion  of  the  eye,  and  its  basal  cells  contain  pigment.  The 
yellow  appearance  of  the  exposed  portion,  often  most  pronounced  near 
the  medial  border  of  the  cornea,  and  known  as  pinguecula,  is  said  not  to 
be  due  to  fat  or  to  an  epithelial  pigment;  it  accompanies  a  thickening  of 
the  connective  tissue  layer.  The  tunica  propria  forms  well-marked 
papillae  near  the  cornea.  Its  lymphocytes  may  form  nodules,  as  many  as 
twenty  having  been  found  in  the  human  conjunctiva  bulbi.  Occasional 


463 


mucous  glands  occur.  (It  may  be  noted  that  the  entire  anterior  cover- 
ing of  the  bulb  of  the  eye  is  named  by  some  the  conjunctiva  bulbi,  which 
accordingly  is  divided  into  the  conj.  sclera  and  the  conj.  cornea.) 

Superior 

tarsal  Radiations 

muscle.  from  the  tendon  Orbicularis 

Conjunctiva.  of  the  levator  palpebrae.     palpebrarum.  Skin. 


...  Oblique  section  of 
a  hair  sheath. 


Cross  section  of  the 
bundles  of  the 

orbicularis 
palpebrarum. 


Arcus  tarseus. .. 


Part  of  a 

ciliary  gland. 


._  Cilium. 


Posterior  edge  of  the  lid. 


Musculus  ciliaris  (Riolani). 


FIG.  469. — SAGITTAL  SECTION  OF  THE  UPPER  LID  OF  A  CHILD  OF  Six  MONTHS.     The  outlet  of  the  tarsa 
gland  was  not  in  the  plane  of  section.     X    15. 

At  the  medial  angle  of  the  lids  there  is  a  thin  fold  of  connective  tissue 
covered  with  stratified  epithelium;  this  plica  semilunaris  is  a  rudimentary 
third  lid.  The  nodular  elevation  of  tissue  at  the  medial  angle,  the  carun- 
cula  lacrimalis,  resembles  skin  except  that  a  stratum  corneum  is  lacking; 


464 


HISTOLOGY 


it  contains  fine  hairs,  sebaceous  and  accessory  lachrymal  glands,  and  in  its 
middle  part,  small  sweat  glands. 

The  blood  vessels  of  the  lids  proceed  from  branches  approaching  the 
lateral  and -medial  angles  of  the  eye.  They  form  an  arch,  the  arcus  tar- 
sens  externus,  at  the  upper  border  of  the  tarsus,  and  a  second  arcus  tarseus 
near  the  free  margin  of  the  lid  (Fig.  469).  They  extend  also  into  the  con- 
junctiva bulbi,  and  near  the  margin  of  the  cornea  they  pass  inward  to 
unite  with  the  anterior  ciliary  vessels  (Fig.  467).  The  lymphatic  vessels 
form  a  close  network  beneath  the  palpebral  conjunctiva,  and  a  loose  one 
in  front  of  the  tarsus.  Whether  the  lymphatic  vessels  of  the  conjunctiva 
bulbi  end  blindly  toward  the  cornea  or  connect  with  the  canaliculi,  has 
not  been  determined.  The  nerves  form  a  very  thick  plexus  in  the  tarsus 
and  supply  the  tarsal  glands.  There  are  free  endings  in  the  conjunctival 
epithelium,  and  bulbous  corpuscles  in  the  connective  tissue  beneath. 


A 


LACHRYMAL  GLANDS. 

The  lachrymal  glands  are  groups  of  compound  tubular  glands,  and  are 
therefore  provided  with  several  excretory  ducts.  These  are  line.d  with  a 
double  row  of  epithelial  cells,  the  superficial  layer  being  columnar.  The 

excretory  ducts  pass  gradu- 
ally into  long  intercalated 
ducts  with  a  low  epithelium. 
These  terminate  in  tubules, 
surrounded  by  a  membrana 
propria,  and  containing  two 
sorts  of  cells.  Certain  cells 
are  tall  when  filled  with  se- 
cretion, which  occupies  the 
superficial  half  of  the  cell; 
when  empty  they  are  shorter. 
The  cells  of  the  other  form 
low  when  full  of  secre- 


•«* 


FIG.  470. — FroM  A  SECTION  OF  A  HUMAN  LACHRYMAL  GLAND. 
X  420. 


are 


A,  Gland  body;  af  tubule  cut  across;  a',  group  of  tubules  cut 
obliquely;  s,  intercalated  tubule;  s',  intercalated  tubule 
in  cross  section;  b,  connective  tissue.  B,  cross  section 

of  an  excretory  duct;  e,  two-rowed   cylindrical    epithe-        .•          wVnVVi  o-athpr<;in   A  lfl.ro-p 
hum;  b,  connective  tissue.  UOn,  WniCn  gamers  in  d,  ld,rgC 

round  mass,  leaving  only  a 

thin  basal  layer  of  protoplasm.  Intercellular  secretory  capillaries  and 
secretory  granules  have  been  demonstrated.  Between  the  gland  cells  and 
the  basement  membrane  there  are  occasional  flat  cells,  which  are  a  con- 
tinuation of  the  deeper  layer  of  the  epithelium  of  the  duct.  The  blood 
vessels  and  nerves  are  similar  to  those  of  the  oral  glands. 

At  the  medial  angle  of  either  eye  there  are  two  lachrymal  ducts  which 
have  no  connection  with  the  lachrymal  glands,  but  serve  to  convey  the 
secretions  which  pass  across  the  front  of  the  eye  to  the  lachrymal  sacs. 


EYE  465 

From  these  sacs  it  passes  through  the  naso-lachrymal  ducts  into  the  nasal 
cavity.  The  lachrymal  ducts  are  lined  with  stratified  squamous  epithe- 
lium, resting  upon  a  tunica  propria  containing  an  abundance  of  cells  and 
elastic  fibers.  Externally  these  ducts  are  surrounded  by  striated  muscle 
fibers,  chiefly  longitudinal.  The  lachrymal  sac,  which  is  provided  with 
small  branched  tubular  glands,  and  the  naso-lachrymal  duct  are  both 
lined  with  two-rowed  columnar  epithelium,  surrounded  by  a  lymphoid 
tunica  propria.  They  are  separated  from  the  underlying  periosteum  by 
a  thick  plexus  of  veins. 

EAR. 

Development  and  General  A  natomy.  The  ear  is  divided  into  three  parts : 
(i)  the  external  ear,  which  includes  the  auricles  projecting  from  the  surface 
of  the  body,  and  the  external  acoustic  meatus  leading  from  the  surface  to 
the  tympanic  membrane',  (2)  the  middle  ear,  including  the  tympanic  cavity 
or  "drum"  and  the  chain  of  three  bones  extending  across  it;  and  (3)  the 
internal  ear,  which  is  a  system  of  epithelial  ducts  and  surrounding  tissue 
spaces,  imbedded  in  the  temporal  bone,  and  connected  with  terminal 
branches  of  the  acoustic  nerve. 

On  either  side  of  the  body,  the  internal  ear  first  appears  as  a  local 
thickening  of  the  epidermal  ectoderm  near  that  portion  of  the  medullary 
tube  which  later  becomes  the  pons.  The  thickened  areas  are  invaginated 
as  shown  in  Fig.  471  A  and  B,  and  the  pockets  thus  produced  become 
separated  from  the  epidermis  in  the  form  of  auditory  vesicles  (otocysts). 
The  place  where  they  become  detached  from  the  epidermis  is  marked 
by  a  slight  elevation  on  the  medial  surface  of  the  vesicle,  which  soon 
elongates,  producing  the  tubular  endolymphatic  duct  (Fig.  471,  C).  The 
blind  upper  end  of  the  duct  becomes  enlarged  to  form  the  endolymphatic 
sac,  which,  however,  is  only  slightly  developed  in  man;  it  appears  in  the 
models  of  the  embryonic  vesicle  shown  in  side  view  in  Fig.  472,  A-C.  In 
the  adult  the  endolymphatic  duct  is  a  very  slender  tube,  terminating 
blindly  (or  perhaps  with  secondary  apertures)  just  beneath  the  dura. 

In  two  places  the  medial  and  the  lateral  walls  of  the  upper  half  of  the 
vesicle  approach  one  another,  and  after  fusing,  the  epithelial  plates  thus 
produced  become  thin  and  rupture,  so  that  two  semicircular  ducts  are  formed 
(Fig.  472,  B  and  C).  The  space  encircled  by  each  duct  may  be  regarded 
as  a  hole  through  the  vesicle.  The  two  ducts  are  the  superior  and  posterior 
semicircular  ducts  respectively.  The  third  or  lateral  semicircular  duct  forms 
soon  afterward.  In  Figs.  471,  D  and  472,  B  it  is  a  horizontal  shelf-like 
projection  of  the  vesicle,  the  center  of  which  is  to  become  perforated  so 
that  its  rim  will  become  the  duct.  The  portion  of  the  vesicle  which  re- 
ceives the  terminal  openings  of  the  three  semicircular  ducts  is  called  the 
30 


466 


HISTOLOGY 


utriculus.  Since  at  one  of  their  ends  the  superior  and  posterior  ducts  unite 
in  a  single  stalk  before  entering  the  utriculus,  there  are  but  five  openings 
for  the  three  ducts  (Fig  472,  D).  Near  one  end  of  each  duct  there  is  a 
dilatation  or  ampulla,  where  nerves  terminate. 


FIG.  471. — SECTIONS  OF  RABBIT  EMBRYOS  TO  SHOW  THE  DEVELOPMENT  OF  THE  EAR.     X  9. 
A,  9  days.  3.8  mm.;  B,  10   days,  3.4  mm.;  C,  12$  days,  7-5  mm.;  D,  14  days,  10  mm.     a.,  Ectodermal 
epithelium  which  forms  the  membranous  internal  ear;  a.  bas.,  basilar  artery;  ch.  t.,  chorda  tympani- 
d.  c.,  cochlear  duct;  d.  e.,  endolymphatic  duct;  d.  s.  1.,  lateral  semicircular  duct;  d.  s.  s.,  superior  semi- 
circular duct;  ep.,  epidermis;  fa.,  facial  nerve;  meten.,  metencephalon;  m.  t.    medullary  tube-  oh 
pharynx. 


d.S.p. 


D 


FIG.  472. — LATERAL  OR  EXTERNAL  SURFACES  OF  MODELS  OF  THE  MEMBRANOUS  PORTION  OF  THE  LEFT 

INTERNAL  EAR  FROM  HUMAN  EMBRYOS.     Different  enlargements.     (After  His,  Jr.) 
A,  from  an  embryo  of  6.9  mm.;  B,  10.2  mm.;  C,  13.5  mm.;  and  D,  22  mm.     am.,  ampulla;  c   v.,  caecum 

vestibulare  of  d.  c., _cochlear  duct;  d.  e.,  endolymphatic  duct;  d.  s.  1.,  d.  s.  p.,  and  d.  s.  s.,  lateral, 

posterior,  and  superior  semicircular  ducts;  sac.,  sacculus;  ut.,  utriculus. 

While  the  formation  of  the  semicircular  ducts  is  occurring  in  the  upper 
part  of  the  auditory  vesicle,  the  lower  portion  elongates  and  its  end  be- 
comes coiled,  eventually  making  two  and  a  half  revolutions.  The  coiled 


EAR 


467 


tube  is  the  ductus  cochlearis;  its  distal  end  is  the  ccecum  cupulare,  and  at  its 
proximal  end  is  the  cacum  vestibulare  (Fig.  472,  D,  c.  v.).  A  dilated  sac 
formed  at  its  proximal  or  upper  end,  opposite  the  caecum  vestibulare,  is 
known  as  the  sacculus;  in  the  adult  the  connection  between  the  sacculus 
and  ductus  cochleae  is  relatively  narrow,  and  is  called  the  ductus  reuniens 
(Fig.  481).  The  portion  of  the  original  vesicle  between  the  sacculus  and 
utriculus,  from  which  the  endolymphatic  duct  arises,  becomes  a  compara- 
tively slender  tube,  the  ductus  utriculo-saccularis  (Fig.  481). 

The  ectodermal  vesicle  thus  produces  a  complex  system  of  connected 
epithelial  ducts,  namely  the  superior,  posterior,  and  lateral  semicircular 


Semicircular  duct. 


Blood  vessel. 


Wall  of  the  semi-"- 
circular  duct. 


r* — — — «  Epithelium  of  the  duct. 


----«*«  Ligament  of  the  duct. 


Bone  of  the  semicircu- 
/  lar  canal. 


Ligament. 


Perilymph  spaces*.,— 


Blood  vessel. 

FIG.  473- — CROSS  SECTION  OF  A  SEMICIRCULAR  DUCT  AND  THE  ADJACENT  PERILYMPH  SPACES   TOGETHER 
WITH  THE  SEMICIRCULAR  CANAL  OF  BONE  IN  WHICH  THEY  ARE  LODGED.     From  a  human  adult.      X  50. 

(Bohm  and  von  Davidoff.) 

ducts;  the  utriculus,  and  utriculo-saccular  duct  with  the  endolymphatic 
duct  connected  with  it;  the  sacculus,  ductus  reuniens  and  ductus  cochleae. 
They  all  contain  a  fluid  called  endolymph.  The  acoustic  nerve  sends 
branches  between  the  epithelial  cells  in  certain  parts  of  the  ducts.  Round 
areas  of  neuro-epithelium,  in  which  the  nerves  terminate,  are  called 
macula  acustica;  there  is  one  in  the  sacculus  and  another  in  the  utriculus. 
Elongated  areas  are  cristce,  and  there  is  one  in  each  of  the  three  ampullae. 
The  axis,  or  modiolus,  about  which  the  cochlear  duct  is  wound,  contains 
the  nerves  which  send  terminal  fibers  to  the  spiral  organ  of  the  adjoining 
epithelium.  In  this  they  form  a  line  of  terminations  along  the  medial 
wall  of  the  cochlear  duct,  following  its  windings  from  base  to  cupola. 


468 


HISTOLOGY 


The  mesenchyma  immediately  surrounding  the  entire  system  of  ducts 
becomes  mucoid  in  appearance,  and  cavities  lined  with  mesenchymal 
epithelium  are  formed  within  it.  They  contain  a  tissue  fluid  called  peri- 
lymph.  Around  the  semicircular  ducts  the  perilymph  spaces  are  so  large 
that  the  tissue  between  them  is  reduced  to  strands  as  shown  in  Fig.  473 ; 
these  are  sometimes  called  ligaments.  The  perilymph  spaces  around  the 
semicircular  ducts  are  irregularly  arranged  and  communicate  with  one 
another  at  various  points;  they  connect  also  with  the  perilymph  cavities 
of  the  vestibule,  which  is  the  central  part  of  the  internal  ear,  from  which 
the  semicircular,  cocblear  and  endolymphatic  ducts  proceed  outward. 
All  of  these  structures  are  surrounded  by  spaces,  connecting  with  those  of 
the  vestibule  which  enclose  the  sacculus  and  utriculus.  At  the  distal 


Modiolus. 
\ 


Scala  vestibuli. 


Ganglion 
spirale. 


Macula. 


Ganglion 
vestibulare. 


Scala  tympani. 


^  Ramus 
cochlearis. 

^  Ramus 
vestibularis. 


of  the  nervus 
acusticus. 


Meatus  acusticus  internus. 

FIG.  474. — HORIZONTAL  SECTION  OF  THE  COCHLEA  OF  A  KITTEN.     X  8. 

The  winding  ductus  cochlearis,  x,  crossed  the  plane  of  section  five  times.     Above  it  in  every  case  is  the 
scala  vestibuli,  and  below  it  is  the  scala  tympani. 

end  of  the  endolymphatic  duct,  the  spaces  communicate  with  those  of 
the  cerebral  arachnoid,  and  the  perilymph  mingles  with  cerebro-spinal 
fluid. 

Around  the  cochlear  duct  the  perilymph  spaces  form  a  single  tube. 
Starting  from  the  vestibule,  it  ascends  to  the  cupola,  following  the  windings 
of  the  cochlear  duct,  to  which  it  is  closely  applied.  It  is  known  as  the 
scala  vestibuli  (i.e.,  "staircase  of  the  vestibule/'  from  which  it  passes  out). 
At  the  apex  of  the  cochlea  it  turns  and  becomes  the  descending  scala 
tympani,  which  ends  blindly  at  the  base  of  the  cochlea,  close  against 
the  wall  of  the  tympanum.  The  two  scalae  bear  a  constant  relation  to  the 
coils  of  the  cochlear  duct.  If  the  cochlea  is  so  placed  that  its  apex  is 
upward,  the  scala  vestibuli  is  always  found  on  the  upper  side  of  the 
duct,  and  the  scala  tympani  on  the  lower  side,  as  shown  in  Fig.  474.  In 
the  body,  the  apex  of  the  cochlea  is  directed  forward  and  outward. 

The  temporal  bone  develops  from  the  mesenchyma  surrounding  the 


EAR  469 

ducts  and  their  perilymph  spaces,  so  that  when  the  membranous  labyrinth 
which  they  form,  is  removed  by  maceration,  the  bone  still  contains  a 
corresponding  arrangement  of  cavities  and  canals.  These  constitute  the 
bony  labyrinth.  Casts  of  it,  made  in  soft  metal,  may  be  seen  in  all  anatom- 
ical museums.  Instead  of  subdivisions  to  correspond  with  the  utriculus, 
sacculus,  and  utriculo-saccular  duct,  the  bony  labyrinth  has  a  single  space, 
already  referred  to  as  the  vestibule.  Into  it  the  semicircular  and  cochlear 
canals  open,  together  with  the  aqu&ductus  vestibuli  which  contains  the 
endolymphatic  duct. 

The  middle  ear  and  external  ear  arise  in  connection  with  the  first  or 
spiracular  gill  cleft.  In  common  with  the  other  clefts,  this  includes  an 
entodermal  pharyngeal  outpocketing  (Fig.  206,  p.  217)  and  an  ectodermal 
depression  (Fig.  205,  sp.}.  At  an  early  stage  these  meet  one  another  and 
fuse,  but  later,  the  primary  epithelial  connection  breaks  down,  and 
mesenchyma  intervenes.  In  the  adult,  however,  the  two  parts  are  still 
close  together,  being  separated  by  only  the  drum  membrane,  which  is 
covered  on  one  side  with  ectoderm  and  on  the  other  with  entoderm. 

The  ectodermal  groove  becomes  surrounded  by  several  nodular  eleva- 
tions of  skin,  which  coalesce  in  a  definite  manner  to  make  the  projecting 
auricle  (pinna).  Its  depression  deepens,  becoming  the  external  acoustic 
meatus,  which  extends  inward  to  the  tympanic  membrane.  The  entoder- 
mal portion  of  the  spiracular  cleft  becomes  in  the  adult  an  elongated 
outpocketing  of  the  pharynx,  known  as  the  auditory  tube  (Eustachian 
tube).  As  seen  in  the  section  Fig.  475,  the  tube  is  separated  from  the 
bottom  of  the  meatus  by  a  very  thin  layer  of  mesenchyma,  which  is  later 
included  in  the  drum  membrane. 

In  the  mesenchyma  behind  the  spiracular  cleft,  a  chain  of  three  small 
bones  (the  malleus,  incus,  and  stapes)  develops;  it  extends  from  the 
meatus  to  the  vestibule.  The  bony  wall  of  the  vestibule  is  deficient 
at  the  small  oval  area  where  the  stapes  reaches  it,  so  that  the  chain  of  bones 
comes  directly  in  contact  with  the  fibrous  covering  of  the  perilymph  space. 
This  area  of  contact  is  thefenestra  veslibuli  (i.e.,  window  of  the  vestibule). 
When  the  chain  of  bones  vibrates  back  and  forth,  the  motion  of  the  stapes 
is  transmitted  through  the  fenestra  vestibuli  to  the  perilymph,  and  waves 
may  pass  up  the  seal  a  vestibuli  and  down  the  scala  tympani,  stimulating 
the  nerves  of  hearing  in  the  cochlear  duct.  The  blind  termination  of 
the  scala  tympani  rests  against  the  lateral  wall  of  the  vestibule,  where  also 
the  bone  fails  to  develop ;  the  round  fenestra  cochlea  is  thus  produced.  Its 
fibrous  membrane  may  yield  somewhat  to  the  perilymph  waves,  thus 
relieving  tension  in  the  cochlea. 

In  Fig.  475  the  fragments  of  the  chain  of  bones  together  with  neigh- 
boring nerves  are  imbedded  in  a  mass  of  mesenchyma.  In  a  later  stage 
the  outer  end  of  the  auditory  tube  expands,  filling  all  the  space  between 


470  HISTOLOGY 

the  vestibule  and  the  bottom  of  the  meatus.  Thus  it  forms  the  tympanic 
cavity.  It  encounters  the  chain  of  bones  and  the  chorda  tympani,  and 
wraps  itself  around  them  so  that  they  lie  in  its  folds  or  plica.  Thus  all 
structures  which  extend  into  the  tympanic  cavity,  or  appear  to  cross  it, 
are  covered  with  a  layer  of  entodermal  epithelium  derived  from  the  audi- 
tory tube.  The  original  contact  between  the  ectoderm  and  entoderm 
of  the  spiracular  cleft  forms  only  an  insignificant  part  of  the  tympanic 
membrane.  The  latter  becomes  greatly  enlarged,  extending  somewhat 
along  the  upper  surface  of  the  ectodermal  auditory  meatus.  The  portion 
of  the  malleus  lying  near  it  becomes  imbedded  in  its  mesenchymal  layer, 


d.s.p. 


d.c.'  ':%;-;v-V 

FIG    475. — HORIZONTAL  SECTION  THROUGH  THE  EAR  OF  A  HUMAN  EMBRYO  OF  ABOUT  5  CMS. 
au.,  Auricle;    au.t.,  auditory  tube;  ch.t.,  chorda    tympani;    d.c.,  cochlear  duct;  d.s.l.,  and  d.s.p.,  lateral 
and  posterior  semicircular  ducts;  e.a.m.,  external  acoustic  meatus;  fa.,   facial  nerve;    f.c.,  fenestra 
cochleae;  p.s.,  perilymphatic  space;  St.,  stapes;  s.tr.,  transverse  sinus;  t.b.,  temporal  bone. 

and  its  inner  entodermal  layer  is  made  by  the  expansion  of  the  tympanic 
cavity.  The  enlargement  of  the  tympanic  cavity  continues  after  birth, 
when  it  invades  the  spaces  formed  within  the  mastoid  part  of  the  temporal 
bone. 

In  spite  of  these  modifications  the  course  of  the  spiracular  cleft  is 
retained  in  the  adult.  The  ectodermal  depression  and  its  surrounding 
elevations  constitute  the  external  ear;  the  pharyngeal  outpocketing  per- 
sists as  the  auditory  tube  and  the  tympanic  cavity  of  the  middle  ear.  It 
opens  freely  into  the  pharynx  and  contains  air. 

SACCULUS,  UTRICULUS,  AND  SEMICIRCULAR  DUCTS. 

The  walls  of  all  these  structures  consist  of  three  layers.  On  the  out- 
side there  is  connective  tissue  with  many  elastic  fibers  and  occasional  pig- 


EAR  '  471 

ment  cells.  This  is  followed  by  a  narrow  basement  membrane  said  to 
form  small  nodular  elevations  toward  the  third  and  innermost  layer,  the 
simple  flat  epithelium.  Near  the  maculae  and  cristae  the  connective  tissue 
and  the  basement  membrane  become  thicker,  and  the  epithelial  cells  are 
columnar  with  a  cuticular  border.  In  the  neuro-epithelium  of  these 
areas  there  are  two  sorts  of  cells,  sustentacular  and  hair  cells.  The  sus- 
tentacular  or  fiber  cells  extend  clear  across  the  epithelium  and  are  some- 
what expanded  at  both  ends;  they  contain  oval  nuclei.  Hair  cells,  which 
receive  the  stimuli,  are  columnar  cells  limited  to  the  superficial  half  of  the 
epithelium;  they  have  large  spherical  nuclei  near  their  rounded  basal  ends, 
and  a  clump  of  fine  agglutinated  filaments  projecting  from  their  free  sur- 
face. The  nerves  lose  their  myelin  as  they  enter  the  epi- 
thelium  and  ascend  to  the  bases  of  the  hair  cells.  There  ** 

they  bend  laterally,  forming  a  dense  network  which  ^ 

appears  as  a  granular  layer  in  ordinary  preparations;  ^>  ^ 

the    granules    are    optical    sections    and  varicosities.  £  ^ 

The  horizontal  fibers  terminate  like  their  occasional     FIG. 
branches,  by  ascending  between  the  hair  cells,  on  the 


sides  of  which  they  form  pointed  free  endings.  They 
do  not  reach  the  free  surface  of  the  epithelium.  This  surface  is  covered  by 
a  continuation  of  the  cuticula,  a  "membrana  limitans,"  which  is  perforated 
by  the  hairs.  Over  the  two  maculae  there  is  a  soft  substance  containing 
very  many  crystals  of  calcium  carbonate,  1-15  ju  long,  which  are  named 
otoconia.  (Large  "ear  stones"  of  fishes  are  called  otoliths.)  Over  the 
cristae  of  the  semicircular  ducts  there  is  a  gelatinous  substance,  transparent 
in  fresh  preparations,  but  coagulated  and  rendered  visible  by  reagents. 

The  "  ligaments  "  of  the  ducts,  the  thin  periosteum  of  the  bony  semi- 
circular canals,  and  the  perilymph  spaces  lined  with  mesenchymal  epithe- 
lium are  seen  in  Fig.  473. 

COCHLEA. 

The  relation  between  the  ductus  cochleae  and  the  scalae  tympani  and 
vestibuli  is  shown  in  Fig.  474.  The  ductus  is  triangular  in  cross  section, 
being  bounded  on  its  peripheral  surface  by  the  thick  periosteum  of  the 
bony  wall  of  the  cochlea;  on  its  apical  surface  (toward  the  cupola)  by  the 
membrana  vestibularis  (Reissner's  membrane)  ;  and  on  its  basal  or  medial 
surface  by  the  lamina  spiralis.  These  three  walls  may  be  described  in 
turn. 

The  peripheral  wall  of  the  cochlear  duct  is  formed  by  the  dense  fibrous 
periosteum  attached  to  the  bone,  together  with  a  large  mass  of  looser 
tissue  crescentic  in  cross  section,  the  ligamentum  spirale  (Fig.  477).  The 
spiral  ligament  is  covered  by  a  layer  of  cuboidal  epithelial  cells  belonging 


472 


HISTOLOGY 


to  the  cochlear  duct.  Close  beneath  the  epithelium  there  are  blood  vessels 
which  are  said  to  give  rise  to  the  endolymph.  The  thick  plexus  which 
they  form  is  described  as  a  band,  the  stria  vascularis,  which  terminates 
more  or  less  distinctly  with  the  vas  prominent.  The  latter  occupies  a  low 
elevation  of  tissue  which  has  its  maximum  development  in  the  basal  coil 
of  the  cochlea  (Fig.  477). 

The  apical  wall,  or  membrana  vestibularis,  consists  of  a  thin  layer  of 
connective  tissue  bounded  on  one  side  by  the  mesenchymal  epithelium 
of  the  scala  vestibuli,  and  on  the  other  by  the  simple  flattened  ectodermal 
epithelium  of  the  cochlear  duct. 


Blood  vessels. 


Scala  vestibuli. 


Ductus 
>^'  cochlearis. 


Vas  prominens 


X  Ligamentum 
spirale. 


Lamina  spiralis  membranacea. 


Ganglion  spirale. 


Scala  tympani. 


Lamina  spiralis  ossea. 


FIG.  477-  —  THE  PORTION  OF  FIGURE  474  MARKED  "SCALA  VESTIBULI"  AND  "SCALA  TYMPANI."     X  50. 

The  basal  wall  or  lamina  spiralis  extends  outward  from  the  modiolus 
to  the  bony  wall  of  the  cochlea.  Near  the  modiolus  it  lies  between  the 
two  scalae,  but  peripherally  it  is  between  the  cochlear  duct  and  the  scala 
tympani.  Toward  the  modiolus  it  contains  a  plate  of  bone  perforated 
for  the  passage  of  vessels  and  nerves;  this  part  is  the  lamina  spiralis  ossea. 
The  peripheral  portion  is  the  lamina  spiralis  membranacea.  Both  parts 
are  covered  below  by  the  mesenchymal  epithelium  of  the  scala  tympani, 
and  above  by  the  epithelium  of  the  cochlear  duct,  including  its  complex 
neuro-  epithelium  known  as  the  spiral  organ  (of  Corti). 

Where  the  membrana  vestibularis  meets  the  osseous  spiral  lamina,  there 
is  an  elevation  of  tough  connective  tissue  called  the  limbus  spiralis  (Fig. 
477).  It  consists  of  abundant  spindle-shaped  cells,  and  blends  below  with 
the  periosteum  of  the  spiral  lamina.  Superficially  it  produces  irregularly 


EAR 


473 


hemispherical  papillae  covered  with  simple  flat  epithelium,  found  within 
the  cochlear  duct  near  the  vestibular  membrane.  Further  within  the 
cochlear  duct  the  papillae  give  place  to  a  single  row  of  flat  ridges  or  plates, 
directed  peripherally.  These  are  "Huschke's  auditory  teeth"  (Fig.  480). 
Beneath  them  the  limb  us  terminates  abruptly  in  an  overhanging  labium 
vestibulare,  which  projects  over  an  excavation — the  sulcus  spiralis  (Fig. 
478).  The  basal  wall  of  the  sulcus  is  the  labium  tympanicum,  found  at 
the  peripheral  edge  of  the  osseous  spiral  lamina.  As  the  epithelium  of 
the  limbus  passes  over  the  labium  vestibulare  into  the  sulcus,  it  becomes 
cuboidal.  A  remarkable  non-nucleated  structure  projects  from  the  labium 

Capillaries  of  the  stria. 


Membrana  tectoria. 
r 

Hair  cells. 


Labium  vestibulare. 

\ 


>:" 


Nerve  bundle. 


1 

Labium 
tympanicum. 


FIG.  478. — PORTION  OF  FIGURE  477. 


Deiter's    Membrana    Connective 

cells.         basilaris.  tissue. 

Pillar  cells. 
X  240.     x,  Intercellular  "tunnel"  traversed  by  nerve  fibers. 


vestibulare  over  the  neuro-epithelium  of  the  membranous  spiral  lamina. 
It  is  called  the  membrana  tectoria  and  is  considered  to  be  a  cuticular  for- 
mation of  the  labial  cells,  to  which  it  is  attached.  Hardesty  describes 
it  as  composed  of  "multitudes  of  delicate  fibers  of  unequal  length,  em- 
bedded in  a  transparent  matrix  of  a  soft,  collagenous  semi-solid  character, 
with  marked  adhesiveness"  (Amer.  Journ.  Anat.,  1908,  vol.  8,  pp.  109-179). 
The  lamina  spiralis  membranacea,  or  lamina  basilaris,  consists  of  four 
layers.  The  mesenchymal  epithelium  of  the  scala  tympani  is  followed  by 
a  layer  of  delicate  connective  tissue,  prolonged  from  the  periosteum  of  the 
scala.  Its  spindle  cells  are  at  right  angles  with  the  fibers  of  the  overlying 
membrana  basilaris.  This  membrane,  which  is  beneath  the  epithelium  of 
the  cochlear  duct,  consists  of  coarse  straight  fibers  extending  from  the  labium 
tympanicum  to  the  ligamentum  spirale.  They  cause  it  to  appear  finely 
striated  (Fig.  479).  Peripherally  (beyond  the  bases  of  the  outer  pillar 
cells)  the  fibers  are  thicker,  and  are  called  "auditory  strings'7;  they  are 


474  HISTOLOGY 

shortest  in  the  basal  part  of  the  cochlea  and  longest  toward  the  apex, 
corresponding  in  length  with  the  basal  layer  of  the  cochlear  duct.  These 
fibers  have  been  thought  to  vibrate  and  assist  in  conveying  sound  waves 
to  the  nerves,  but  theories  which  assume  that  the  basilar  membrane  is 
a  "vibrating  mechanism"  are  considered  untenable  by  Hardesty;  he  finds 
it  more  probable  that  the  membrana  tectoria  vibrates  and  transmits 
stimuli  to  the  neuro-epithelium. 

The  epithelial  cells  covering  the  basilar  layer  occur  in  rows  of  highly 
modified  forms,  which  extend  up  and  down  the  cochlear  duct,  constituting 
the  spiral  organ  (organ  of  Corti).     Next  to  the  cuboidal  epithelium  of 
the  sulcus  spiralis  there  is  a  single  row  of  inner  hair  cells 
(Fig.  480).     These  are  short  columnar  cells  which  do 
not  reach  the  bottom  of  the  epithelium;  each  has  about 
forty  long  stiff  hairs  on  its  free  surface.     The  inner 
hair  cells  are  followed  peripherally  by  two  rows  of 
pillar  cells,  the  inner  and  outer,  which  extend  the  whole 
length  of  the  cochlear  duct.     As  seen  in  cross  section 
FIG.  479.— SURFACE     they  are  in  contact  above,  but  are  separated  below  by 
LAMINA  SPIRALIS     a   triangular  intercellular  space  or  "tunnel."  which  is 

MEMBRANACEA  OF  .  . 

A  CAT.     x  240.     filled  with  soft  intercellular  substance.     Thus  they  rest 

Drawnwitb  J 

change  of  focus.       upon  the  basilar  membrane  in  A -form.     Each  pillar 

e,  Epithelium  (  cells  of  .    . 

Claudius)  of  the     cell  may  be  subdivided  into  a  head,  a  slender  body. 

ductus    cochleans  »  ^  J  ' 

of  theUmembinra     an<^  an  expanded  triangular  base.     The  greater  portion 

bfs nuc?ein of octhci     of  eacn  cel1  nas  been  transformed  into  a  resistant  band, 

Sec^vJtifsue0.011"     at  the  base  of  which,  within  the  tunnel,  there  is  a  mass 

of  protoplasm  containing  the  nucleus.     A  protoplasmic 

sheath  extends  up  from  the  base  around  the  body  of  the  cell.     Dark  round 

structures  which  may  be  found  in  the  heads  of  the  pillars,  and  at  the 

foot  of  the  outer  ones,  are  not  nuclei,  but  are  "probably  of  horny  nature. " 

The  heads  of  the  pillars  interlock.     Both  pillars  produce  "head-plates" 

directed  outward,  and  so  arranged  that  the  plate  from  the  inner  pillar 

overlies  that  from  the  outer  pillar  (Fig.  480).     Moreover,  the  round  head 

of  the  outer  pillar  is  fitted  into  a  concavity  in  the  head  of  the  inner  pillar, 

as  shown  in  the  figure. 

On  the  peripheral  side  of  the  outer  pillars  there  are  several  rows 
(usually  four)  of  outer  hair  cells  separated  from  one  another  by  sustentacu- 
lar  cells  (Deiter's  cells).  The  outer  hair  cells  have  shorter  hairs  than  the 
inner  ones,  and  are  characterized  by  the  presence  of  "Hensen's  spiral 
bodies,"  one  of  which  occurs  in  the  outer  half  of  each  cell.  These  bodies, 
shown  as  dark  spots  in  Fig.  480,  probably  represent  a  trophospongium. 
The  centrosomes  of  the  hair  cells  are  always  in  their  upper  ends.  Like 
the  inner  hair  cells,  the  outer  ones  do  not  extend  to  the  basilar  membrane, 
thus  leaving  unoccupied  the  communicating  intercellular  spaces  between 


EAR 


475 


the  deeper  portions  of  the  sustentacular  cells.     These  Nuel's  spaces  connect 
with  the  tunnel. 

Deiter's  sustentacular  cells  are  slender  bodies,  each  containing  a  stiff 
filament,  and  having  at  its  free  end  a  cuticular  formation  referred  to  as  a 
"phalanx."  The  phalanges  come  between  the  outer  hair  cells,  separating 
them  from  one  another  (Fig.  480),  and  the  inner  hair  cells  are  similarly 
separated  by  short  processes — the  inner  phalanges,  derived  from  the  inner 
pillars.  (The  inner  phalanges  are  not  shown  in  the  figure.)  The  phalanges 
of  Deiter's  cells  connect  with  one  another,  forming  a  trim  reticular  mem- 
brane. As  a  whole  Deiter's  cells  resemble  the  pillar  cells,  but  their  trans- 
formation into  stiff  fibers  has  not  proceeded  so  far;  the  cuticular  border  is 
comparable  with  the  head  plate. 


I 

Nerve. 


Tun- 
.    nel. 
Vas  spirale 


Inner 


Outer 


Nuel's 
space. 


Membrana  Tympanal 
Deiter's    basilaris.    lamella, 
cells. 


Pillar  cells. 

FIG.  480. — DIAGRAM  OF  THE  STRUCTURE  OF  THE  BASAL  WALL  OF  THE  DUCT  OF  THE  COCHLEA. 
A,  View  from  the  side.     B,  View  from  the  surface.     In  the  latter  the  free  surface  is  in  focus.     It  is  evident 
that  the  epithelium  of  the  sulcus  spiralis,  lying  in  another  plane,  as  well  as  the  cells  of  Claudius,  can 
be  seen  distinctly  only  by  lowering  the  tube.     The  membrana  tectoria  is  not  drawn.     The  spiral 
nerves  are  indicated  by  dots. 

The  most  peripheral  of  the  sustentacular  or  Deiter's  cells  are  followed 
by  elongated  columnar  cells  (cells  of  Hensen),  which  gradually  shorten, 
and  are  succeeded  by  the  low  "cells  of  Claudius"  which  extend  to  the 
limit  of  the  membrana  basilaris.  In  both  the  columnar  and  the  low  forms 
there  are  single  stiff  filaments  which  are  less  developed  than  in  the  susten- 
tacular cells.  The  centrosomes  of  all  these  cells  lie  near  their  free  surfaces. 
Beyond  the  basilar  membrane  the  epithelium  is  continued  over  the 
ligamentum  spirale  as  a  layer  of  cells  with  branching  basal  processes 
extending  deep  into  the  underlying  tissue. 


476  HISTOLOGY 

NERVES  OF  THE  LABYRINTH. 

The  acoustic  nerve  is  a  purely  sensory  nerve  passing  between  the  pons 
and  internal  ear  through  a  bony  canal,  the  internal  acoustic  meatus.  It  is 
divided  into  vestibular  and  cochlear  portions  (Fig.  474).  The  vestibular 
nerve  proceeds  from  the  vestibular  ganglion  and  has  four  branches — the 
utricular  nerve  and  the  superior,  lateral,  and  posterior  ampullary  nerves; 
according  to  Streeter  (Amer.  Journ.  Anat.,  1906,  vol.  6,  pp.  139-165)  it 
produces  also  the  branch  to  the  sacculus,  usually  regarded  as  derived 
from  the  cochlear  nerve.  If  this  is  true,  the  cochlear  nerve  supplies 
only  the  spiral  organ  of  Corti.  The  ganglion  of  the  cochlear  nerve  is 
lodged  within  the  modiolus  at  the  root  of  the  lamina  spiralis,  and  is  known 
as  the  spiral  ganglion  (Figs.  474  and  477).  The  ganglion  cells  remain 
bipolar,  like  those  of  embryonic  spinal  ganglia.  They  are  surrounded  by 
connective  tissue  capsules;  and  their  neuraxons  and  single  peripheral 
dendrites  receive  my  elm  sheaths  not  far  from  the  cell  bodies. 

The  peripheral  fibers  extend  through  the  lamina  spiralis  ossea,  within 
which  they  form  a  wide-meshed  plexus,  and  after  losing  their  myelin  they 
emerge  from  its  outer  border  in  the  labium  tympanicum  through  the 
foramina  nervosa.  In  continuing  to  the  spiral  organ  they  curve  in  the 
direction  of  the  cochlear  windings,  thus  producing  spiral  strands.  Those 
nearest  the  modiolus  are  on  the  axial  side  of  the  pillar  cells;  the  middle 
ones  are  between  the  pillars,  in  the  tunnel;  and  the  outer  ones  are  beyond 
the  pillar  cells.  From  these  bundles,  delicate  fibers  pass  to  the  hair  cells, 
on  the  sides  of  which  they  terminate. 

VESSELS  OF  THE  LABYRINTH. 

The  internal  auditory  artery  is  a  branch  of  the  basilar  artery.  It 
arises  in  connection  with  branches  which  are  distributed  to  the  under 
side  of  the  cerebellum  and  the  neighboring  cerebral  nerves,  and  passes 
through  the  internal  acoustic  meatus  to  the  ear.  It  divides  into  vestibular 
and  cochlear  branches  (Fig.  481).  The  vestibular  artery  supplies  the 
vestibular  nerve  and  the  upper  lateral  portion  of  the  sacculus,  utriculus 
and  semicircular  ducts.  The  cochlear  artery  sends  a  vestibulo-cochlear 
branch  to  the  lower  and  medial  portion  of  the  sacculus,  utriculus,  and  ducts. 
This  branch  also  supplies  the  first  third  of  the  first  turn  of  the  cochlea. 
The  capillaries  formed  by  the  vestibular  branches  are  generally  wide 
meshed,  but  near  the  maculae  and  cristae  the  meshes  are  narrower.  The 
terminal  portion  of  the  cochlear  artery  enters  the  modiolus  and  forms  three 
or  four  spirally  ascending  branches.  These  give  rise  to  about  thirty  radial 
branches  distributed  to  three  sets  of  capillaries  (Fig.  482);  i,  those  to  the 
spiral  ganglion;  2,  those  to  the  lamina  spiralis;  and  3,  those  to  the  outer 
walls  of  the  scalae  and  the  stria  vascularis  of  the  cochlear  duct. 


EAR 


477 


The  veins  of  the  labyrinth  form  three  groups  (Fig.  481).  i.  The  vena 
aquceduclus  vestibuli  receives  blood  from  the  semicircular  ducts  and  a  part 
of  the  utriculus.  It  passes  toward  the  brain  in  a  bony  canal  along  with 
the  ductus  endolymphaticus,  and  empties  into  the  superior  petrosal  sinus. 
2.  The  vena  aquaductus  cochlea  receives  blood  from  parts  of  the  utriculus, 
sacculus  and  cochlea;  it  passes  through  a  bony  canal  to  the  internal 
jugular  vein.  Within  the  cochlea  it  arises,  as  shown  in  Fig.  482,  from 


rteria  auditiva    {  Arteria  vestibularis. 
interna  ,  Arteria  cochlearis. 


Ductus  semicircularis 
superior. 

Ampulla  lateralis. 


Vena  aquaeductus 
vestibuli. 

Ductus  semicircularis 
lateralis. 


rteria  /      Superior     Inferior     Anterior  Posterior          Ampulla          Ductus  semicircularis 

ilearis.  /  posterior.  posterior. 

Vestibulo-cochlear    * • •    * « ; ' 

branch  of  the  Vena  spinalis.  Vena  vestibularis. 

arteria  cochlearis.       « • ' 

Vena  aquaeductus  cochleae. 

;.  481. — DIAGRAM  OF  THE  BLOOD  VESSELS  OF  THE  RIGHT  HUMAN  LABYRINTH.    MEDIAL  AND  POSTERIOR  ASPECT. 
,  c.,  Ductus  cochlearis;  S.,  sacculus;  U.;  utriculus;  i,  ductus  reunions;  2,  ductus  utriculo-saccularis.     The  saccus 

endolymphaticus  is  cut  off. 

small  vessels  including  the  vas  prominens  (a)  and  the  vas  spirale  (b). 
Branches  derived  from  these  veins  pass  toward  the  modiolus.  (There  are 
no  vessels  in  the  vestibular  membrane  of  the  adult,  and  the  vessels  in  the 
wall  of  the  scala  tympani  are  so  arranged  that  only  veins  occur  in  the  part 
toward  the  membranous  spiral  lamina;  thus  the  latter  is  not  affected  by 
arterial  pulsation.)  Within  the  modiolus  the  veins  unite  in  an  inferior 
spiral  vein,  which  receives  blood  from  the  basal  and  a  part  of  the  second 
turns  of  the  cochlea,  and  a  superior  spiral  vein  which  proceeds  from  the 


478 


HISTOLOGY 


apical  portion.  These  two  spiral  veins  unite  with  vestibular  branches  to 
form  the  vena  aquaeductus  cochleae  (Fig.  481).  3.  The  internal  auditory 
vein  arises  within  the  modiolus  from  the  veins  of  the  spiral  lamina;  these 
anastomose  with  the  spiral  veins  (Fig.  482).  It  receives  branches  also 
from  the  acoustic  nerve  and  from  the  bones,  and  empties  "in  all  prob- 
ability, into  the  vena  spinalis  anterior/' 

Lymphatic  spaces  within  the  internal  ear  are  represented  by  the  peri- 
lymph  spaces,  which  communicate  through  the  aquaeductus  cochleae  with 

Scala  tympani.     Scala  vestibuli. 


Stria  vasculars. 


Cross  section  of  a  spiral 
/artery  of  the  modiolus. 


..--'Vena  laminae  spiralis. 


•  Ganglion  spirale. 


Vena  spiralis  superior. 


Cross  section  of  a  spiral 
artery  of  the  modiolus. 


Vena  laminae  spiralis. 


""  Anastomosis. 


. Vena  spiralis  inferior. 


FIG.  482. — DIAGRAM  OF  A  SECTION  OF  THE  FIRST  (BASAL)  AND   SECOND  TURNS  OF  THE  COCHLEA. 
a,    Vas  prominens;  b,  vas  spirale. 

the  arachnoid  space;  the  connecting  structure,  or  "ductus  perilym- 
phaticus,"  is  described  as  a  lymphatic  vessel.  The  saccus  endolymph- 
aticus,  which  is  the  dilated  distal  end  of  the  endolymphatic  duct,  is  in  con- 
tact with  the  dura,  and  there  are  said  to  be  openings  between  it  and  the 
subdural  space.  In  the  internal  ear  perivascular  and  perineural  spaces 
are  found,  and  they  probably  connect  with  the  arachnoid  spaces. 


MIDDLE  EAR. 

The  tympanic  cavity,  which  contains  air,  is  lined  with  a  mucous  mem- 
brane closely  connected  with  the  surrounding  periosteum.     It  consists  of 


EAR 


479 


a  thin  layer  of  connective  tissue,  covered  generally  with  simple  cuboidal 
epithelium.  In  places  the  epithelial  cells  may  be  flat,  or  tall  with  nuclei 
in  two  rows.  Cilia  are  sometimes  widely  distributed  and  are  usually  to 
be  found  on  the  floor  of  the  cavity.  In  its  anterior  part,  small  alveolar 
mucous  glands  occur  very  sparingly.  Capillaries  form  wide-meshed  net- 
works in  the  connective  tissue,  and  lymphatic  vessels  are  found  in  the 
periosteum. 

The  auditory  tube  includes  an  osseous  part  toward  the  tympanum,  and 
a  cartilaginous  .part  toward  the  pharynx.  Its  mucosa  consists  of  fibrillar 
connective  tissue,  together  with  a  ciliated  columnar  epithelium  which 


Cartilage 


Cartilage. ^ 


Mucosa'of  the 
pharynx. 


-., Glands. 


Glands.  ---  CTHI 


FIG.  483. — CROSS  SECTION  OF  THE  CARTILAGINOUS  PART  OF  THE  AUDITORY  TUBE.     X  12. 
(Bohm  and  von  Davidoff.) 


becomes  stratified  as  it  approaches  the  pharynx.  The  stroke  of  the  cilia 
is  toward  the  pharyngeal  orifice  In  the  osseous  portion,  the  mucosa  is 
without  glands  and  very  thin;  it  adheres  closely  to  the  surrounding  bone. 
Along  its  floor  there  are  pockets  containing  air,  the  cellules  pneumaticcs. 
In  the  cartilaginous  part  the  mucosa  is  thicker;  near  the  pharynx  it  con- 
tains many  mucous  glands  (Fig.  483).  Lymphocytes  are  abundant  in 
the  surrounding  connective  tissue,  forming  nodules  near  the  end  of  the 
tube,  which  blend  with  the  pharyngeal  tonsil.  The  cartilage,  which  only 
partly  surrounds  the  auditory  tube,  is  hyaline  near  its  junction  with  the 
bone  of  the  osseous  portion;  it  may  contain  here  and  there  coarse  fibers 
which  are  not  elastic.  Toward  the  pharynx  the  matrix  contains  thick 
nets  of  elastic  tissue,  and  the  cartilage  is  consequently  elastic. 


480 


HISTOLOGY 


EXTERNAL  EAR. 

Between  the  middle  ear  and  the  external  ear  is  the  tympanic  mem- 
brane, which  consists,  from  without  inward,  of  the  following  strata:  the 
cutaneum,  radiatum,  circular e  and  mucosum  (Fig.  484).  The  stratum 
cutaneum  is  a  thin  skin  without  papillae  in  its  corium,  except  along  the 
handle  or  manubrium  of  the  malleus.  There  it 
is  a  thicker  layer,  containing  the  vessels  and 
nerves  which  descend  along  the  manubrium  and 
spread  from  it  radially.  In  addition  to  the  venous 
plexus  which  accompanies  the  artery  in  that  situa- 
tion, there  is  a  plexus  of  veins  at  the  periphery 
of  the  membrane,  receiving  tributaries  from  both 
the  stratum  cutaneum  and  the  less  vascular  stra- 
tum mucosum.  The  radiate  and  circular  strata 
consist  of  compact  bundles  of  fibrous  and  elastic 
tissue,  arranged  so  as  to  suggest  tendon.  The 
fibers  of  the  radial  layer  blend  with  the  perichon- 
drium  of  the  hyaline  cartilage  covering  the  manu- 
brium. Peripherally  the  fiber  layers  form  a  nbro-cartilaginous  ring  which 
connects  with  the  surrounding  bone.  The  stratum  mucosum  is  a  thin  layer 
of  connective  tissue  covered  with  a  simple  non-ciliated  flat  epithelium 


Epidermis. 


c    d 


FIG.  484. — CROSS  SECTION  OF 
THE  MEMBRANA  TYMPANI 
BELOW  THE  MANUBRIUM. 
X  450.  (After  Kolliker.) 

a,  Stratum  cutaneum  (show- 
ing the  corneum  and 
germinativum) ;  b,  stra- 
tum radiatum,  its  fibers 
cut  across;  c,  stratum  cir- 
culare;  d,  stratum  mu- 
cosum. 


Hair  sheath. 
Corium. 

Excretory  duct. 

Young  hair. 
Coil  of  ceruminous  gland. 


FIG.  485. — FROM  A  VERTICAL  SECTION  THROUGH 

THE      SKIN      OF      THE     EXTERNAL     AUDITORY 

MEATUS  OF  AN  INFANT.     X   50.     The  excre- 
tory duct  opens  into  the  hair  follicle. 


Membrana  propria. 

Nuclei  of  smooth  muscle  fibers. 

Secretion. 

Gland  cells. 


Secretion. 

J  —  Cuticular  border. 

7    .Gland  cells. 

Nuclei  of  smooth  muscle 
_    ^     ^_  fibers. 

— -j  "    Membrana  propria. 

FlG.  486. TUBLES  OF  THE  CERUMINOUS  GLANDS. 

A,  Cross  section,  from  an  infant;  B,  longitu- 
dinal section,  from  a  boy  12  years  old. 


continuous  with  the  lining  of  the  tympanic  cavity.  Peripherally,  in 
children,  its  cells  may  be  taller  and  ciliated.  As  a  whole  the  tympanic 
membrane  is  divided  into  tense  and  flaccid  portions.  The  latter  is  a  rela- 
tively small  upper  part  in  which  the  fibrous  layers  are  deficient. 


EAR  ;      481 

The  external  acoustic  meatus  is  lined  with  skin  continuous  with  the 
cutaneous  layer  of  the  tympanic  membrane.  In  the  deep  or  osseous  por- 
tion the  skin  is  very  thin,  -without  hair  or  glands  except  along  its  upper 
wall.  There  and  in  the  outer  or  cartilaginous  part,  ceruminous  glands  are 
abundant.  "They  are  branched  tubulo-alveolar  glands"  (Huber)  which 
in  many  respects  resemble  large  sweat  glands.  Their  ducts  are  lined  with 
stratified  epithelium.  The  coils  consist  of  a  single  layer  of  secreting  cells, 
general  cuboidal,  surrounded  by  smooth  muscle  fibers  and  a  well-defined 
basement  membrane.  They  differ  from  sweat  glands  in  that  their  coils 
have  a  very  large  lumen,  especially  in  the  adult;  and  their  gland  cells, 
often  with  a  distinct  cuticular  border,  contain  many  pigment  granules  and 
fat  droplets.  Their  narrow  ducts  in  adults  end  on  the  surface  of  the  skin 
close  beside  the  hair  sheaths;  in  children  they  empty  into  the  sheaths 
(Fig.  485).  It  has  not  been  shown  that  the  ceruminous  glands  are  more 
directly  concerned  in  the  production  of  cerumen  than  the  sebaceous 
glands.  The  cerumen  obviously  is  an  oily  rather  than  a  watery  secre- 
tion, and  it  contains  fatty  cells  and  pigment. 

The  cartilage  of  the  external  acoustic  meatus  and  of  the  auricle  is 
elastic. 

NOSE. 

The  nasal  cavities  are  formed  by  the  invagination  of  a  pair  of  epi- 
dermal thickenings  similar  to  those  which  give  rise  to  the  lens  and  auditory 
vesicle.     The  pockets  thus  produced  in  the  embryo  are  called  "nasal  pits" 
(Fig.  205,  n,  p.  216).     Their  external  openings 
remain  as  the  nares  of  the  adult,  but  tempor- 
arily, from  the  third  to  the  fifth  month  of  em- 
bryonic life,   they  are  closed   by  an  epithelial 
proliferation.     Each  nasal  pit  acquires  an  in- 
ternal opening,  the  ckoana,  in  the  roof  of  the 
pharynx.     The   choanae   are   at   first  situated 
near  the  front  of  the  mouth,  separated  from 
one  another  by  a  broad  nasal  septum  (Fig.  487). 
As  the  latter  extends  posteriorly,  it  is  joined  by 

.  .     ,  FIG.    487.— THE    ROOF    OF    THE 

the  palate  processes  which  grow  toward  it  from         MOUTH  OF  A  HUMAN  EMBRYO 

OF   8   WEEKS.     X    4.    (After 

the  sides  of  the  maxillae.     Thus  the  choanae  re-         Koiimann.) 

na,  Naris;  ch.,  choana;  al.  p.,  i.  p., 

Cede     tOWard     the     back     Of      the     mOUth     While  and  pa.  p.,  alveolar,  intermax- 

illary, and  palate  processes. 

the  embryonic  condition  of  cleft  palate  is  being 

removed  (Fig.  488) .  The  lateral  walls  of  the  nasal  cavities  produce  three 
curved  folds  one  above  another;  they  are  concave  below,  and  in  them 
the  concha  (turbinate  bones)  develop.  The  nasal  mucosa  covers  these 
and  extends  into  excavations  in  the  adjacent  bones,  forming  the  sphenoid, 
31 


482 


HISTOLOGY 


maxillary,  and  frontal  sinuses,  and  the  ethmoidal  cells.  The  boundary  be- 
tween the  epithelium  of  the  nasal  pit  and  that  of  the  pharynx  early  disap- 
pears, and  the  extent  of  each  in  the  adult  is  uncertain.  Presumably  the  ol- 
factory neuro-epithelium  is  derived  from  the  nasal  pit.  In  man  the  olfac- 
tory region  is  limited  to  the  upper  third  of  the  nasal  septum  and  nearly  the 
whole  of  the  superior  concha  (Read).  This  regio  olfactoria  is  covered  by  a 
yellowish-brown  membrane,  which  may  be  distinguished  macroscopically 
from  the  reddish  mucosa  of  the  regio  respiratoria.  The  latter  includes  the 
remainder  of  the  nose.  The  two  regions  may  be  considered  in  turn. 

The  vestibule,  or  cavity  of  the  projecting  cartilaginous  portion  of  the 
nose,  is  a  part  of  the  respiratory  region  which  is  lined  with  a  continuation 


Dental  ridge 

of  the  \      |* 

upper  jaw. 


Oral 
epithelium. 


Dental  ridge  |Ui 

of  the 
lower  jaw. 


Cartilaginous 
nasal  septum. 


Nasal  cavity. 


Maxilla. 


Oral  cavity. 


Tongue. 


Mandible. 


FIG.  488.— FRONTAL  SECTION  OF  THE  HEAD  OF  A  40-MM.    SHEEP  EMBRYO.     X  15. 

The  palate  processes  have  united  with  the  nasal  septum.  The  conchse  are  developing  along  the  lateral 
walls  of  the  nasal  cavity.  In  the  lower  part  of  the  nasal  septum  the  vomero-nasal  organs  are  seen  as  a 
pair  of  tubes,  each  of  which  is  partly  surrounded  by  a  crescentic  cartilage. 

of  the  skin.  Its  stratified  epithelium  has  squamous  outer  cells  and  rests 
upon  a  tunica  propria  with  papillae.  It  contains  the  sheaths  of  coarse 
hairs  (vibrissa)  together  with  numerous  sebaceous  glands.  The  extent 
of  the  squamous  epithelium  is  variable;  frequently  it  is  found  on  the 
middle  concha,  less  often  on  the  inferior  concha. 

The  remainder  of  the  respiratory  mucosa  consists  of  a  pseudo-stratified 
epithelium  with  several  rows  of  nuclei.  It  may  contain  few  or  many 
goblet  cells.  The  tunica  propria  is  well  developed,  being  even  4  mm. 
thick  on  the  inferior  concha  (Fig.  489).  It  consists  of  fibrillar  tissue  with 
many  elastic  elements,  especially  abundant  in  its  deeper  layers.  Beneath 
the  epithelium,  it  is  thickened  to  form  a  homogeneous  membrana  propria, 


NOSE 


483 


perforated  with  small  holes.  Lymphocytes  are  present  in  variable  quan- 
tity, sometimes  forming  solitary  nodules  and  often  entering  the  epithelium 
in  great  numbers.  Branched  alveolo-tubular  mixed  glands  extend  into 
the  tunica  propria.  Their  serous  portions  have  intercellular  secretory 
capillaries,  and  both  mucous  and  serous  cells  contain  a  trophospongium. 
The  glands  often  empty  into  funnel-shaped  depressions,  which  are  macro- 
scopic on  the  inferior  concha,  and  are  lined  with  the  superficial  epithelium. 


Epithelium 


Tunica 
propria. 


Vein 


-i&^^^W 

||i^%^-.._.. 


Mucous 
.  cells. 


Serous 
cells. 


Artery. 


t Bone. 


FIG.  489. — VERTICAL  SECTION  THROUGH  THE  MUCOSA  OF  THE  INFERIOR  CONCHA  OF  MAN.  X  48.  On 
the  left  is  a  funnel-shaped  depression  receiving  an  excretory  duct;  near-by  on  the  right  is  the  section 
of  a  large  vein. 

The  mucosa  of  the  several  paranasal  sinuses  is  thin  ( — o.o2mm.),  with 
less  elastic  tissue  and  but  few  small  glands.  A  pocket  which  extends 
into  the  lower  part  of  the  median  septum  has  already  been  described 
as  the  vomero-nasal  organ  (Jacobson's  organ).  In  man  it  is  the  rudimen- 
tary remnant  of  an  important  sense  organ,  supplied  by  special  branches 
of  the  olfactory  nerves  and  by  the  nervus  terminalis  (cf.  p.  141).  It 
is  lined  with  a  tall  columnar  epithelium,  and  contains,  at  least  in  the 


484 


HISTOLOGY 


cat,  "sensory  cells  apparently  identical  with  those  of  the  olfactory 
mucosa."  In  man  sensory  cells  are  said  to  be  lacking  in  the  adult  and 
in  embryos  older  than  five  months. 

In  the  regio  olfactoria  the  mucosa  includes  a  tunica  propria  and  an 

olfactory  epithelium.  The  latter  consists  of 
sustentacular  cells  and  olfactory  cells.  The 
superficial  halves  of  the  sustentacular  cells 
are  cylindrical,  and  contain  yellowish  pig- 
ment, together  with  small  mucoid  granules 
often  arranged  in  vertical  rows  (Fig.  490). 
The  more  slender  lower  halves  have  den- 
tate or  notched  borders,  and  branched 
basal  ends  which  unite  wkh  those  of  neigh- 
boring cells,  thus  forming  a  protoplasmic 
network.  Their  nuclei,  generally  oval,  are 
in  one  plane  and  in  vertical  sections  they 
form  a  narrow  "zone  of  oval  nuclei" 
(Fig.  491).  The  olfactory  cells  generally 

have  round  nuclei  containing  nucleoli.  They  occur  at  different  levels 
and  so  form  a  broad  ''zone  of  round  nuclei."  From  the  protoplasm 


FIG.  490. — ISOLATED  CELLS  OF  THE  OL- 
FACTORY MUCOSA  OF  A  RABBIT. 
X  560. 

st,  Supporting  cells;  s,  extruded  mucus 
resembling  cilia;  r,  olfactory  cells,  from 
r'  the  lower  process  has  been  torn  off;  f , 
ciliated  cell;  b,  cells  of  olfactory  glands. 


Wandering  cell.          Mucus. 


Excretory  duct. 


Pigment 
granules. 

Oval  nucleus  of 

a  sustentacular 

cell. 

Round  nucleus 

of  an  olfactory 
cell. 
Basal  cell. 


Sections  of  olfactory  glands. 

Dilated  duct.  Mucus. 

FIG.  4Qi. — VERTICAL  SECTION  THROUGH  THE  OLFACTORY  REGION  OF  AN  ADULT.     X  400. 

which  is  gathered   immediately  about   the  nucleus,  each  olfactory  cell 
sends  a  slender   cylindrical    process  toward   the   surface,  where  it   ter- 


NOSE 


485 


minates  in  a  variety  of  ways.  It  may  end  in  a  small  knob-like  swelling, 
or  in  a  single  slender  spine ;  sometimes  the  terminal  knob  sends  out  a  small 
cluster  of  divergent  olfactory  hairs  or  spines.  Basally  the  olfactory  cells 
pass  directly  into  the  axis  cylinders  of  the  olfactory  nerves  (Fig.  492). 
Thus  they  are  ganglion  cells,  their  basal  processes  being  neuraxons.  Cells 
intermediate  between  the  olfactory  and  sustentacular  forms  may  be  found, 
and  these  are  doubtless  imperfectly  developed  sensory  cells.  At  the  free 
surface  of  the  olfactory  epithelium  there  are  terminal  bars,  and  small 
projecting  strands  of  mucus,  sometimes  suggesting  cilia  (Fig.  490,  s). 


Central  ependymal 

cells. 


Fibers  of  the  olfac- 
tory tract. 


Mitral  cells. 


Glomeruli. 


Olfactory  nerves. 


Olfactory  fibers  in 

the    nasal    mucous 

membrane. 

Olfactory  cells. 


PIG.  492. — CHIEF  ELEMENTS  OF  THE  OLFACTORY  BULB.     (Gordinier,  after  Van  Gehuchten.) 

The  mucus,  which  is  the  product  of  the  sustentacular  cells,  may  appear  to 
form  a  continuous  superficial  membrane  (Fig.  491).  Near  the  tunica 
propria  there  is  a  network  of  so-called  " basal  cells"  (Fig.  491). 

The  tunica  propria  is  composed  of  fibrous  tissue  and  fine  elastic- 
fibers,  associated  with  many  connective  tissue  cells.  In  some  animals 
(for  example,  the  cat)  it  forms  a  structureless  membrane  next  to  the  epi- 
thelium. It  surrounds  the  numerous  olfactory  glands  (Bowman's  glands). 
In  man  these  consist  of  excretory  ducts  extending  through  the  epithelium, 
and  of  branching  gland  bodies  beneath.  They  have  the  appearance  of 
serous  glands,  but  sometimes  contain  mucus,  generally  in  small  quantities. 
They  are  found  not  only  in  the  olfactory  region,  but  also  in  the  adjoining 
part  of  the  respiratory  region. 


486  HISTOLOGY 

The  deeper  layers  of  the  tunica  propria  contain  the  arteries  of  the 
mucous  membrane,  which  send  branches  toward  the  epithelium,  and 
form  a  thick  sub-epithelial  plexus  of  capillaries.  The  veins  are  very 
numerous,  especially  at  the  inner  end  of  the  inferior  concha,  where  the 
tunica  propria  resembles  cavernous  tissue.  Lymphatic  vessels  form  a 
coarse  meshed  network  in  the  deeper  connective  tissue.  Injections  of  the 
arachnoid  spaces  around  the  olfactory  bulbs  follow  the  perineural  sheaths 
of  the  olfactory  nerves  into  the  nasal  mucosa,  but  these  tissue  spaces  are 
not  lymphatic  vessels. 

The  olfactory  nerves,  as  already  stated,  are  formed  of  the  basal  proc- 
esses of  the  olfactory  epithelial  cells,  which  become  non-medullated  nerve 
fibers.  This  is  a  primitive  type  of  nervous  apparatus  (cf.  p.  132),  such  as 
is  not  found  elsewhere  in  the  human  body.  After  a  tangential  course 
beneath  the  epithelium,  the  fibers  unite  in  bundles,  and  pass  through  the 
cribriform  plate  of  the  ethmoid  bone  to  the  olfactory  bulb  just  above  it, 
which  they  enter.  They  spread  tangentially  and  branch,  finally  termi- 
nating in  the  glomeruli.  The  glomeruli  are  round  or  oval  groups  of 
arborizing  fibers,  in  which  the  processes  of  the  olfactory  cells  end  in 
relation  with  the  dendrites  of  the  mitral  cells.  The  latter  are  nerve  cells 
with  triangular  bodies,  which  form  a  characteristic  layer  of  the  olfactory 
bulb,  and  send  their  neuraxons  through  the  olfactory  tracts  to  make 
various  connections  within  the  hemispheres. 

In  addition  to  the  olfactory  nerves,  the  nasal  mucous  membrane  con- 
tains medullated  branches  of  the  trigeminal  nerve,  distributed  both  to  the 
olfactory  and  respiratory  regions. 


PART  II. 

MICROSCOPICAL  TECHNIQUE. 

I.  THE  PREPARATION  OF  MICROSCOPICAL 

SPECIMENS. 

REVISED  BY  LAWSON  G.  LOWREY. 

The  methods  of  fundamental  importance,  which  are  likely  to  be  em- 
ployed by  students  who  are  beginning  their  histological  studies,  are  here 
given.  Further  information  may  be  obtained  from  "The  Microtomist's 
Vade  Mecum"  by  A.  B.  Lee  (Blakiston,  Philadelphia)  and  from  Mallory 
and  Wright's  " Pathological  Technique"  (Saunders,  Philadelphia).  The 
former  deals  with  the  subject  from  the  point  of  view  of  general  biology; 
the  latter  is  particularly  adapted  to  the  needs  of  medical  students. 

FRESH  TISSUES. 

Certain  tissues  may  be  studied  advantageously  in  a  fresh  condition. 
They  are  simply  spread  on  a  clean  glass  slide,  covered  and  examined. 
Desquamated  epithelial  cells,  spermatozoa,  blood,  and  other  fluids  con- 
taining cells,  may  be  treated  in  this  way.  But  structures  such  as  muscles, 
tendons,  nerves,  connective  tissue,  etc.,  must  first  be  "teased" — that  is, 
torn  into  very  small  fragments  or  spread  into  a  thin  layer  with  a  pair  of 
fine  needles. 

The  "parenchymatous"  organs,  or  other  structures  which  cannot  be 
investigated  satisfactorily  by  the  above  methods,  must  be  sectioned  or 
macerated.  The  old  methods  of  making  free-hand  sections  of  the  object 
held  between  pieces  of  pith,  or  of  making  sections  with  a  double  bladed 
knife,  have  been  superseded  in  most  laboratories  by  the  freezing  method. 
This  method  is  often  serviceable  in  histology,  and  is  indispensable  in 
the  rapid  diagnosis  of  pathological  conditions. 

Blocks  of  tissue  not  over  5  mm.  thick  are  moistened  with  water,  placed 
on  the  carrier  of  a  special  form  of  microtome  and  frozen  by  a  jet  of  carbon 
dioxide  proceeding  from  a  tank  of  the  compressed  gas.  Sections  10  to  i5/£ 
thick  may  be  chiselled  from  the  block  of  tissue  and  unrolled  by  transferring 
to  a  dish  of  0.6  per  cent,  sodium  chloride  solution.  They  are  floated  on  a 
slide,  covered  and  examined. 

.      487 


488  HISTOLOGY 

Sections  or  teased  preparations  must  be  kept  moist  during  examination. 
In  order  to  avoid  distortion,  they  are  not  mounted  in  water,  but  in  so- 
called  indifferent  fluids,  such  as  the  lymph,  aqueous  humor,  serous  fluids, 
amniotic  fluid,  etc.  Of  the  artificial  indifferent  media,  a  0.6  per  cent, 
solution  of  sodium  chloride  in  distilled  water  has  been  found  to  cause  less 
distortion  than  the  stronger  fluids  formerly  recommended. 

Ringer's  Solution.  An  indifferent  fluid  which  is  perhaps  more  satis- 
factory than  the  0.6  per  cent,  salt  solution  is  a  modification  of  Ringer's 
solution  adapted  to  the  tissues  of  warm-blooded  animals.  It  is  to  be  made 
in  large  quantities. 

Sodium  chloride 90.0 

Potassium  chloride 4.2 

Calcium  chloride  (anhydrous) 2.4 

Potassium  bicarbonate 2.0 

Distilled  water 10,000. o 

Examination  of  fresh  tissues  reveals  but  little  of  the  fine  details  of 
structure.  Since  the  indices  of  refraction  of  the  different  tissue  elements 
have  much  the  same  value,  outlines  are  usually  dim  and  there  is  very  little 
optical  differentiation.  The  method  of  handling  is  prone  to  produce  dis- 
tortion and  with  many  tissues  and  organs  it  is  difficult  to  separate  their 
constituent  elements.  ^  It  is  generally  necessary  to  employ  more  complex 
methods  of  treatment  to  gain  an  adequate  idea  of  the  histological  details. 

One  of  the  simplest  methods  is  to  add  one  or  two  drops  of  i  to  5  per  cent, 
acetic  acid  solution  to  the  fresh  preparation.  The  nuclei  then  appear  more 
distinctly.  Albuminous  granules  are  dissolved,  but  fat  and  myelin  are  not 
affected.  The  white  fibers  of  connective  tissue  swell  and  disintegrate, 
leaving  the  elastic  fibers  unaffected. 

Nuclei  may  be  rendered  distinct  by  allowing  a  few  drops  of  stain  to  act 
upon  the  tissue  for  a  few  minutes.  A  i  per  cent,  aqueous  solution  of  methy- 
lene  blue,  or  a  i  per  cent,  solution  of  methyl  green  in  20  per  cent,  alcohol, 
or  the  haematoxylin  solutions,  may  be  used. 

ISOLATION. 

Some  tissues  cannot  properly  be  separated  into  their  elements  in  the 
fresh  condition,  but  may  be  shaken  or  teased  apart  after  preliminary 
treatment.  The  reagents  employed  in  maceration  have  the  property  of 
softening  or  removing  certain  constituents  of  the  tissues,  at  the  same  time 
fixing  or  hardening  other  elements.  Usually  the  intercellular  portions  are 
softened  or  removed,  while  the  cellular  elements  undergo  fixation. 

Ranvier  Js  Alcohol.  This  is  a  mixture  of  one  volume  of  95  per  cent,  alcohol 
and  2  volumes  of  distilled  water.  The  cells  of  small  pieces  of  epithelium 
(5-10  mm.  square)  are  separable  in  24  to  48  hours.  They  are  examined 
in  the  same  fluid,  or  washed  in  water  and  examined  in  glycerin. 


MACERATING   FLUIDS  489 

Nitric  Acid  and  Potassium  Chlorate.  About  5  gm.  of  potassium 
chlorate  are  dissolved  in  20  c.c.  of  the  acid.  Muscle  cells  are  separable  in 
one  to  six  hours.  Wash  thoroughly  in  water  and  examine  in  water  or 
glycerin. 

Potassium  Hydrate.  Muscle  cells  may  be  teased  apart  after  immersion 
for  about  an  hour  in  a  35  per  cent,  aqueous  solution.  They  may  be  ex- 
amined in  the  same  solution  or  transferred  to  a  saturated  aqueous  solution 
of  potassium  acetate,  which  prevents  further  maceration.  The  solution 
of  potassium  hydrate  may  also  be  used  for  isolating  epithelial  cells. 

Concentrated  Sulphuric  Acid.  The  elements  of  the  epidermis,  hair  and 
nails  may  be  separated  after  immersion  in  this  fluid.  They  should  be 
thoroughly  washed  in  water. 

PERMANENT  PREPARATIONS/ 

None  of  the  methods  described  above  yield  much  information  re- 
specting the  finer  structure  of  tissues  and  organs,  nor  do  they  yield  perma- 
nent preparations.  For  ease  of  reference,  the  various  steps  in  the  pro- 
duction of  a  permanent  preparation  have  been  grouped  under  the  follow- 
ing five  headings. 

1.  Fixation.     Under  this  heading  are  given  formulae  for  the  best  fixing 
fluids,  with  directions  for  their  use  and  for  the  subsequent  handling  of  the 
tissue  until  it  is  placed  in  80  per  cent,  alcohol,  in  which  tissues  may  be 
kept  for  a  considerable  time. 

2.  Imbedding.     This   includes   the   various   steps   for   preparing   the 
tissues  to  be  sectioned  in  paraffin  or  celloidin,  starting  from  80  per  cent, 
alcohol. 

3.  Cutting  and  handling  sections.     Brief  directions  are  given  for  cutting 
sections  and  handling  them,  until  they  are  ready  for  staining. 

4.  Staining.     Formulae  and  directions  for  the  use  of  stains,  and  the 
after  treatment  until  the  preparation  is  in  the  appropriate  clearing  fluid. 

5.  Clearing  and  mounting.     The  choice  of  a  clearing  agent  for  paraffin 
and  celloidin  sections  is  discussed,  together  with  the  methods  and  media 
for  mounting. 

Since  each  of  the  fixing,  imbedding  and  staining  methods  is  considered 
as  a  unit,  each  starting  where  the  previous  step  ends,  the  student  can 
easily  prepare  specimens  according  to  any  desired  possible  combination 
by  referring  to  the  directions  for  the  selected  fixative,  imbedding  method, 
and  stain. 

i.  Fixation. 

A  good  fixative  should  penetrate  and  kill  tissues  quickly;  preserve  the 
tissue  elements,  particularly  the  nuclei,  in  the  condition  in  which  they  are 


490  HISTOLOGY 

found  at  the  moment  of  its  action;  render  structures  insoluble,  and  harden 
them  so  that  they  will  not  be  altered  by  the  various  after-steps;  and  give 
a  certain  degree  of  optical  differentiation. 

No  single  compound  has  yet  been  found  which  successfully  fulfills  all 
of  these  conditions,  nor  are  any  of  the  recommended  fixatives  adequate 
in  all  cases  or  for  all  special  studies.  Only  the  fluids  commonly  employed, 
which  have  proven  most  useful,  are  here  given. 

Small  pieces  of  tissue,  preferably  less  than  i  cm.  in  thickness,  should 
be  dropped  into  a  considerable  amount  of  fluid.  The  tissue  should  be 
handled  as  little  as  possible,  in  order  that  delicate  structures  may  not  be 
destroyed.  For  example,  contact  between  the  fingers  and  the  peritoneum 
is  sufficient  to  destroy  the  thin  epithelium. 

In  order  to  insure  uniform  action  of  the  fixing  fluid,  it  is  often  advisable 
to  place  a  little  absorbent  cotton  in  the  bottom  of  the  vessel.  Frequent 
gentle  mechanical  agitation  will  serve  the  same  end.  Tubular  organs 
should  be  washed  out,  or  cut  open  and  their  contents  and  any  adherent 
blood  washed  away,  with  salt  solution.  Membranes  may  be  kept  flat 
and  smooth  by  tying  them  across  the  end  of  a  short  tube  or  detached 
bottle  neck. 

Alcohol.  Small  or  thin  pieces  of  tissue  are  supported  on  a  little  ab- 
sorbent cotton  in  absolute  alcohol,  for  12  to  24  hours,  changing  after  3 
or  4  hours.  Large  pieces  are  fixed  by  successive  immersion  in  70  per  cent., 
80  per  cent.,  and  95  per  cent,  alcohol  for  24  hours  each. 

Alcohol  is  a  valuable  dehydrating  and  hardening  agent,  but  its  fixing 
qualities  are  inferior,  so  that  it  is  rarely  used  alone  as  a  fixative.  Small 
embryos  or  blocks  of  tissue  obtained  in  an  emergency  should  be  preserved 
in  10  per  cent,  formalin,  rather  than  in  alcohol. 

Bouin's  Fluid. 

Picric  acid,  saturated  aqueous  solution 75 

Formalin 20 

Glacial  acetic  acid 5 

This  fluid  is  particularly  recommended  for  the  fixation  of  embryos, 
for  which  it  is  unexcelled.  Small  embryos  are  fixed  in  4  to  6  hours.  Larger 
objects  may  be  fixed  24  to  48  hours  or  longer.  For  washing  out  the  fixing 
fluid,  alcohol,  first  70  per  cent.,  then  80  per  cent.,  should  be  employed. 
Renew  the  alcohol  as  often  as  discolored. 

Carney's  Mixtures. 

No.  i — Absolute  alcohol 6 

Chloroform 3 

Glacial  acetic  acid i 

This  is  a  very  rapid  fixative,  even  large  pieces  being  fixed  in  f  to  i 
hour.  Wash  in  absolute  alcohol  until  the  odor  of  acetic  acid  is  lost,  chang- 
ing every  12  hours,  and  imbed;  or  grade  through  95  per  cent,  to  80  per 
cent,  alcohol. 


FIXING    FLUIDS  49 1 

No.  2.  Saturate  mixture  No.  i  with  mercuric  bichloride  (about  20 
parts).  This  is  the  most  rapid  and  penetrating  fixative  known,  and  it 
affords  a  very  delicate  cytological  fixation.  Immersion  for  30  minutes 
to  i  hour  is  sufficient  even  for  the  larger  pieces.  Subsequent  treatment 
as  with  No.  i,  except  that  the  crystals  of  sublimate  must  be  removed  from 
the  tissue,  either  by  placing  the  block  in  80  per  cent,  alcohol  and  iodine 
(see  Zenker's  fluid) ;  or  after  the  block  has  been  cut,  by  treating  the  sec- 
tions with  iodine  (see  p.  497). 

Flemming's  Fluid. 

Osmic  acid,  i  %  aqueous  solution 10 

Chromic  acid,  i  %  aqueous  solution 25 

Glacial  acetic  acid,  i  %  aq.  solution 10 

Distilled  water 55 

This  solution  should  be  mixed  only  at  the  time  of  using.  Only  very 
thin  pieces  (not  over  2  mm.  thick)  should  be  used.  Fix  for  24  hours  or 
longer  (sometimes  even  for  weeks).  Wash  in  running  water  24  hours. 
Pass  through  50  per  cent.,  70  per  cent.  (12  hours  in  each),  to  80  per  cent, 
alcohol. 

Formaldehyde.  The  gas  is  soluble  in  water  to  the  extent  of  40  per 
cent.,  and  solutions  of  this  strength  are  obtainable  under  the  trade  names 
of  formalin,  formol,  and  formalose. 

For  fixing  tissues,  10  c.c.  of  the  commercial  product  are  added  to  90 
c.c.  of  water.  It  penetrates  very  quickly,  but  specimens  may  be  left  in 
it  for  a  considerable  time  without  apparent  harm.  Ordinary  blocks  are 
sufficiently  fixed  in  from  12  to  24  hours.  Transfer  directly  to  80  per  cent, 
alcohol. 

Histologically,  its  chief  use  is  for  the  preservation  of  nervous  tissue, 
the  fixation  of  tissue  to  be  cut  with  the  freezing  microtome,  and  the  preser- 
vation of  embryos.  Small  human  embryos  obtained  by  practitioners  should 
be  put  at  once  into  10  per  cent,  formalin  and  forwarded  to  an  embryological 
laboratory. 

Marchi's  Fluid. 

Potassium  bichromate 2.5 

Sulphate  of  sodium i .  o 

Water 100.0 

Osmic  acid,  i%  aqueous  solution 50.  o 

Small  pieces  are  fixed  for  5  to  8  days  in  the  dark.  Wash  24  hours  in 
running  water;  50  per  cent,  and  70  per  cent,  alcohol  (24  hours  each); 
80  per  cent,  alcohol.  Used  for  demonstrating  degenerated  nerve  fibers 
and  in  making  damar  mounts  of  fat  and  myelin,  since  the  osmium  reduced 
by  fat  is  insoluble  in  alcohol.  Sections  must  not  be  treated  with  xylol, 
but  chloroform  should  be  used  instead. 

Orth's  Fluid. 

Potassium  bichromate 25 

Sodium  sulphate 10 

Water .    1000 


492  HISTOLOGY 

At  the  time  of  using  mix  10  c.c.  of  formalin  with  90  c.c.  of  the  above 
solution  (which  is  known  as  Miiller's  fluid).  Small  pieces  are  fixed  in 
about  48  hours.  Wash  in  running  water  for  12  to  24  hours.  Then  50 
per  cent,  alcohol  and  70  per  cent,  alcohol,  12  to  24  hours  each;  80  per  cent, 
alcohol.  This  is  useful  as  a  fixative  for  the  central  nervous  system,  and 
as  a  general  fixative. 

Zenker's  Fluid. — This  is  kept  in  the  form  of  the  following  stock  solu- 
tion, in  preparing  which  the  water  is  heated  and  the  ingredients  are  stirred 
with  a  glass  rod  (metal  instruments  must  not  be  put  into  this  fluid) . 

Potassium  bichromate 25 

Sodium  sulphate 10 

Mercuric  bichloride 50 

Water , .  1000 

At  the  time  of  using,  add  5  c.c.  of  glacial  acetic  acid  to  95  c.c.  of  the 
above  solution.  The  tissues,  which  float  for  a  short  time,  are  fixed  for 
6  to  24  hours,  after  which  they  are  washed  in  running  water  12  to  24 
hours.  Then  they  are  transferred  to  50  per  cent,  alcohol  for  12  to  24 
hours;  70  per  cent,  alcohol,  12  to  24  hours;  80  per  cent,  alcohol. 

Corrosive  sublimate  forms  crystalline  deposits  in  the  tissues,  and 
these  must  be  removed  before  the  preparation  is  stained.  They  may  be 
removed  by  adding  enough  tincture  of  iodine  to  give  a  port-wine  color 
to  the  70  per  cent,  and  80  per  cent,  alcohols  in  which  the  block  of  tissue 
is  immersed.  More  iodine  is  added  as  the  solution  becomes  colorless 
(or  nearly  so)  and  the  treatment  must  be  continued  until  the  color  no 
longer  changes.  The  tissues  are  then  to  be  placed  in  fresh  80  per  cent., 
renewed  two  or  three  times  in  order  to  remove  completely  the  mercuric 
iodide.  The  crystals  of  sublimate  may  be  removed  after  the  tissue  has 
been  sectioned,  as  described  on  p.  497. 

Zenker's  fluid  is  an  excellent  fixative,  which  penetrates  easily  and 
does  not  decrease  the  staining  qualities.  It  is  probably  the  best  "general 
fixative." 

DECALCIFICATION. 

Specimens  which  contain  bone  or  calcareous  material  cannot  be  sec- 
tioned until  they  have  been  decalcified.  The  tissues  are  fixed,  according 
to  the  directions  given  above,  in  Zenker's  fluid,  Orth's  fluid,  or  formalde- 
hyde, and  hardened.  After  several  days  in  80  per  cent,  alcohol,  they  are 
put  into  a  considerable  quantity  of  3  to  5  per  cent,  aqueous  solution  of 
nitric  acid.  This  should  be  renewed  at  intervals  for  3  or  4  days,  until 
the  bone  can  be  penetrated  easily  with  a  needle.  Wash  in  running  water 
for  a  day,  and  return  to  80  per  cent,  alcohol.  Imbed  in  celloidin. 

Phloroglucin  is  sometimes  added  to  the  decalcifying  fluid  to  protect 
the  tissue.  The  following  solution  has  been  recommended.  It  is  to  be 
used  in  the  same  manner  as  the  aqueous  solution  of  nitric  acid. 


DECALCIFYING    FLUIDS  493 

Phloroglucin i 

Nitric  acid 5 

Alcohol,  95% 70 

Water 30 

The  addition  of  i  or  2  per  cent,  of  nitric  acid  to  the  80  per  cent,  alcohol 
will  decalcify  small  embryos.  The  specimen  should  then  be  thoroughly 
washed  in  fresh  80  per  cent.,  in  order  to  remove  the  acid. 

2.    Imbedding. 

Most  of  the  fixatives  employed  are  in  aqueous  solution.  After  fixa- 
tion and  the  removal  of  the  fixative  by  washing  in  water  or  alcohol,  as 
directed,  the  specimen  must  not  be  left  in  water,  but  must  be  dehydrated. 
Dehydration  has  a  double  purpose:  (i)  to  remove  the  water,  which  espe- 
cially favors  post-mortem  decomposition,  and  (2)  to  prepare  the  tissue 
for  infiltration  with  the  imbedding  'substance  or,  in  the  case  of  objects 
to  be  mounted  whole,  for  infiltration  with  the  mounting  medium. 

All  the  fixation  methods  given  above  end  with  placing  the  block  of 
tissue  in  80  per  cent,  alcohol.  Here  they  may  be  left  until  wanted, 
although  immersion  for  a  considerable  time  causes  a  gradual  loss  in  stain- 
ing qualities.  Stronger  alcohol  causes  an  overhardening,  while  macera- 
tion may  occur  in  weaker  alcohols. 

Dehydration  is  accomplished  by  immersing  the  specimen  in  gradually 
increasing  strengths  of  alcohol.  Those  commonly  employed  are  50  per 
cent.,  70  per  cent.,  80  per  cent.,  95  per  cent,  and  absolute.  The  lower 
grades  may  be  prepared  from  the  ordinary  barrel  alcohol,  of  about  95  per 
cent,  strength,  as  follows: 

80  per  cent. — 425  c.c.  95  per  cent,  alcohol  mixed  with    75  c.c.  distilled  water 
70  per  cent. — 370  c.c.         -       '•  •'  •  •         •«      130  c.c. 

50  per  cent. — 265  c.c.  "     ••       «•          »          ««        ««     235  c.c. 

The  specimen  is  left  in  each  grade  long  enough  to  be  saturated.  The 
time  required  varies  from  3  to  24  hours.  Objects  of  average  size  require 
about  6  to  12  hours.  Prolonged  immersion  in  95  per  cent,  or  absolute  is 
very  injurious  to  the  tissues. 

In  imbedding,  the  tissue  is  surrounded  and  infiltrated  with  a  firm  sub- 
stance which  can  be  cut  into  thin  sections,  supporting  and  holding  firm  the 
fragile  tissue.  Celloidin,  which  is  solid  upon  the  evaporation  of  its  solvent, 
and  paraffin,  which  is  solid  at  ordinary  temperatures,  are  the  substances 
used,  each  having  its  particular  advantages. 

Paraffin  Imbedding.  Specimens  cannot  be  passed  directly  from  al- 
cohol to  paraffin,  since  alcohol  dissolves  only  a  very  little  paraffin  and  the 
specimen  would  not  be  thoroughly  infiltrated.  So  the  specimen  must  first 
be  passed  through  some  fluid  which  mixes  with  absolute  alcohol  and  will 
dissolve  paraffin.  Of  a  host  of  reagents  possessing  this  property,  chloro- 
form is  recommended  for  general  use. 

After  thorough  dehydration  (12-24  hours  in  absolute  alcohol),  the 


494  HISTOLOGY 

specimen  is  passed  from  absolute  to  a  mixture  of  equal  parts  of  absolute 
and  chloroform  for  2  to  6  hours,  and  then  to  pure  chloroform  for  an  equal 
length  of  time.  It  is  then  transferred  to  a  saturated  solution  of  paraffin  in 
chloroform,  kept  warm  by  placing  on  top  of  the  paraffin  bath,  for  2  to  4 
hours,  and  is  then  put  into  melted  filtered  paraffin. 

The  melting  point  of  the  paraffin  used  varies  with  the  temperature  in 
which  it  is  to  be  cut.  During  the  winter,  paraffin  melting  at  5o°-52°  C. 
should  be  used,  while  during  the  summer  paraffin  with  a  melting  point  of 
56°-58°  is  best.  Harder  paraffin  is  required  for  thin  than  for  thick  sec- 
tions. The  melted  paraffin  should  be  kept  in  a  paraffin  bath  or  thermostat 
maintained  at  a  temperature  but  slightly  higher  than  the  melting  point  of 
the  paraffin. 

The  specimen  should  be  left  in  the  melted  paraffin  for  the  shortest  time 
which  will  allow  thorough  infiltration,  as  heat  is  very  injurious  to  the  tissue. 
For  average  specimens,  3  hours  is  sufficient.  Transfer  to  fresh  paraffin 
at  the  end  of  ij  or  2  hours.  At  the  end  of  the  full  time,  the  specimen  is 
to  be  imbedded. 

The  imbedding  frame  consists  of  a  glass  plate  and  two  L-shaped  pieces 
of  metal.  By  sliding  the  latter  back  and  forth  on  one  another,  the  size 
of  the  enclosed  space  or  box  may  be  varied.  Before  using  the  frame, 
the  inner  surfaces  of  the  metal  pieces  and  that  part  of  the  glass  plate  on 
which  they  rest  are  rubbed  with  glycerin.  It  should  form  a  thin  film 
over  the  surfaces,  but  not  accumulate  in  drops.  Melted  paraffin  is 
poured  into  the  box  and  the  specimen  is  transferred  to  it  with  a  spatula. 
The  specimen  sinks  to  the  bottom,  and  may  be  arranged  in  any  desired 
position  by  means  of  needles  warm  enough  to  prevent  the  paraffin  solidify- 
ing over  their  surfaces.  The  paraffin  must  be  quickly  cooled  by  lowering 
the  frame  into  a  basin  of  cold  water  so  that  the  water  comes  up  on  the 
sides  of  the  metal  pieces.  As  soon  as  a  resistant  film  has  formed  over 
the  surface  of  the  paraffin,  the  entire  frame  may  be  submerged,  and  in 
a  few  minutes  the  glass  plate  and  metal  pieces  may  be  detached  from  the 
solid  paraffin.  The  block  may  be  sectioned  as  soon  as  it  is  thoroughly 
cooled. 

When  a  number  of  specimens  are  to  be  imbedded,  a  flat  dish  of  suitable 
size  may  be  used.  After  a  thin  layer  of  glycerin  has  been  coated  over 
the  interior,  the  dish  is  filled  with  a  sufficient  quantity  of  melted  paraffin 
and  the  blocks  are  put  into  position.  The  mass  is  cooled  and  removed 
as  before,  and  the  large  mass  is  cut  into  smaller  parts,  each  containing  a 
specimen. 

One  or  several  specimens  may  be  imbedded  in  paper  boxes  of  suitable 
size.  The  tabs  at  the  ends  may  be  labelled  and  the  specimens  kept  in 
the  boxes  until  wanted;  otherwise  labels  may  be  scratched  in  the  paraffin 
with  needles. 


PARAFFIN   IMBEDDING  495 

Paraffin  imbedding  is  to  be  chosen  when  very  thin  sections  or  serial 
sections  are  desired.  Material  imbedded  in  paraffin  may  be  kept  for 
years  without  any  apparent  deterioration. 

Celloidin  Imbedding.  Thick  celloidin  is  prepared  by  dissolving  30 
gm.  of  Schering's  granular  celloidin  in  300  c.c.  of  a  mixture  of  equal 
parts  of  ether  and  absolute  alcohol.  It  has  a  thick  syrupy  consistency, 
and  becomes  constantly  denser  by  evaporation  of  the  solvent.  It  should 
be  kept  in  a  tightly  closed  preserve  jar.  Thin  celloidin  is  prepared  by 
mixing  equal  volumes  of  the  thick  celloidin  and  the  absolute  and  ether 
mixture. 

The  hardened  and  dehydrated  block  of  tissue,  trimmed  to  the  size 
and  shape  desired,  is  transferred  from  absolute  alcohol  to  a  mixture  of 
equal  parts  of  ether  and  absolute  for  24  hours.  From  this  it  is  transferred 
to  thin  celloidin,  in  which  it  remains  from  24  hours  to  a  week  or  longer, 
and  then  to  thick  celloidin  for  the  same  length  of  time.  The  success 
of  the  process  depends  largely  upon  the  thorough  infiltration  of  the 
tissue  with  the  celloidin.  The  time  required  in  the  celloidin  varies  with 
the  penetrability  of  the  tissue  and  the  size  of  the  piece. 

After  remaining  for  a  sufficient  length  of  time  in  the  thick  celloidin, 
the  tissue  is  taken  out  with  a  mass  of  adherent  celloidin  and  is  pressed 
gently  against  the  roughened  surface  of  a  block  of  vulcanized  fiber. 
As  soon  as  a  film  has  formed  upon  the  surface,  the  block  and  attached 
specimen  are  dropped  into  80  per  cent,  alcohol,  in  which  the  mass  becomes 
firm.  It  is  ready  for  sectioning  in  about  6  hours. 

In  case  it  is  desired  to  secure  sections  through  the  entire  thickness 
of  the  specimen,  the  following  method  is  recommended.  A  sufficient 
quantity  of  thick  celloidin  is  poured  into  a  flat  dish  (or  paper  box)  and 
the  specimen  is  put  into  it.  The  entire  mass  is  hardened  as  before  and 
then  a  block  of  celloidin  containing  the  specimen  is  cut  out.  This  is 
trimmed  to  leave  only  a  thin  rim  around  the  specimen.  The  block  is 
placed  for  a  few  moments  in  the  ether-absolute  mixture,  and  then  dipped 
in  thick  celloidin  and  pressed  against  the  surface  of  a  fiber  block,  which 
has  also  been  dipped  in  the  ether- absolute  mixture  and  in  thick  celloidin. 
The  mass  is  allowed  to  harden  somewhat,  and  then  is  placed  in  80  per 
cent,  alcohol. 

The  imbedded  specimen  is  kept  in  80  per  cent,  alcohol  until  wanted 
for  sectioning.  Celloidin  imbedding  is  recommended  for  large  objects, 
or  for  those  from  which  very  thin  sections  are  unnecessary. 

RESUME"  OF  IMBEDDING  METHODS. 

Assuming  that  the  tissues  have  been  fixed  and  carried  into  80  per 
cent,  alcohol,  the  steps  in  imbedding  are  as  follows: 


496  HISTOLOGY 

Paraffin  Celloidin 

95  per  cent,  alcohol 12-24  hr.  95  per  cent,  alcohol 12-24  hr. 

Absolute 12-24  hr.  Absolute 12-24  hr. 

Absolute  and  chloroform,  equal  parts.  2-  6  hr.  Absolute  and  ether,  equal 

Chloroform 2-  6  hr.  parts 12-24  hr. 

Chloroform  saturated  with  paraffin.    2-  4  hr.  Thin  celloidin 24  hr.  to  a  week 

Melted  paraffin 2-  4  hr.  Thick  celloidin 24  hr.  to  a  week 

Imbed  in  fresh  melted  paraffin  and  cool  quickly.  Mount  on  fiber  block;  harden  and  preserve  in 

80  per  cent,  alcohol. 


3.  Cutting  and  Handling  Sections. 

Paraffin  Sections.  Two  kinds  of  microtomes  are  in  general  use  for 
sectioning  objects  imbedded  in  paraffin.  In  one  form,  the  "precision 
microtome,"  the  knife  is  horizontally  placed  and  the  object  is  moved 
backward  and  forward  on  a  carrier.  In  the  rotary  microtome,  the  knife 
is  vertically  placed  and  the  object  is  moved  up  and  down,  being  cut  on 
the  down  stroke.  In  both  forms,  the  knife  edge  is  at  right  angles  to  the 
carrier  and  the  object. 

For  sectioning  with  the  precision  microtome,  the  object  is  mounted  on 
a  fiber  block  which  is  then  clamped  in  the  microtome;  with  the  rotary 
form,  it  is  mounted  on  a  special  metal  disc.  Before  attaching  the  im- 
bedded object,  superfluous  paraffin  is  cut  away,  leaving  the  tissue  rising 
from  a  broad  base  and  completely  surrounded  by  a  thin  layer  of  paraffin. 
The  block  should  be  trimmed  so  as  to  give  a  rectangular  or  square  surface 
to  be  cut,  and  there  should  be  a  considerable  layer  of  paraffin  between  the 
object  and  the  block  or  disc  to  which  it  is  to  be  attached.  The  base  is 
placed  upon  a  heated  spatula  which  rests  upon  the  fiber  block.  When 
the  paraffin  is  somewhat  melted,  the  spatula  is  withdrawn  and  the  base 
is  pressed  down  upon  the  block,  to  which  it  adheres  when  the  paraffin 
solidifies.  In  mounting  upon  the  metal  disc,  the  disc  is  heated,  the  block 
pressed  upon  it  and  the  whole  quickly  cooled  by  immersing  in  water. 

If  the  paraffin  on  each  side  of  the  object  is  trimmed  parallel  with  the 
knife  edge,  the  successive  sections  adhere  to  one  another,  forming  ribbons. 
As  they  are  taken  from  the  knife,  the  ribbons  are  laid  in  a  shallow  box. 
By  placing  them  in  order,  they  may  later  be  attached  to  the  slide  in  per- 
fect series,  one  after  the  other.  The  first  one  cut  is  attached  to  the  upper 
left  hand  corner,  and  the  others  follow  like  lines  on  a  printed  page.  Sec- 
tions mounted  in  this  way  are  called  serial  sections.  The  sections  should 
be  from  5  to  10  ^  in  thickness,  but  under  favorable  conditions  thinner 
sections  may  be  secured. 

Before  they  can  be  stained,  paraffin  sections  must  be  attached  to  the 
slide  and  the  paraffin  must  be  removed.  To  attach  them  to  a  slide,  a 
mixture  of  equal  parts  of  white  of  egg  and  glycerin  is  used.  The  white 
of  egg  is  thoroughly  stirred  and  filtered.  An  equal  volume  of  glycerin  is 
added,  the  two  thoroughly  mixed  and  a  small  lump  of  camphor  added  as 


PARAFFIN   SECTIONS-  497 

a  preservative.  The  mixture  is  kept  in  a  glass-capped  bottle,  with  a 
glass  rod  for  a  dropper. 

A  drop  is  placed  upon  a  thoroughly  clean  slide  and  rubbed  evenly 
with  the  finger  (freed  from  oil)  over  all  the  area  upon  which  sections  may 
be  placed.  It  should  be  free  from  bubbles  and  should  make  a  very  thin 
layer,  just  thick  enough  to  allow  the  finger  to  glide  easily  over  the  surface 
of  the  slide.  A  few  drops  of  water  are  placed  upon  it,  forming  a  layer  over 
the  albumen  deep  enough  to  float  the  paraffin  sections,  strips  of  which 
are  placed  upon  the  water.  The  shiny  side  of  the  ribbon  should  rest  upon 
the  water.  The  slide  is  then  held  for  a  moment  over  the  flame  of  an  alco- 
hol lamp  so  that  the  water  is  heated.  Repeat  until  the  sections  become 
perfectly  smooth  and  flat,  but  the  paraffin  must  not  be  melted.  The  water 
should  not  come  in  contact  with  the  fingers  holding  the  slide.  If  the  al- 
bumen layer  ends  abruptly  before  reaching  the  border  of  the  slide,  the 
water  will  not  so  readily  spread  beyond  it.  After  the  flattening  process, 
the  water  is  cautiously  drained  off  by  a  moist  sponge  held  at  the  corner 
of  the  slide.  The  sections  settle  down  upon  the  albumen  and  may  be 
arranged  in  straight  lines  with  needles  applied  to  the  paraffin,  but  not  to 
the  tissues  of  the  sections.  The  slide  is  then  held  vertically  in  contact  with 
filter  paper  to  drain  off  any  water  which  may  remain,  and  the  portions 
of  the  slide  which  are  free  from  sections  are  wiped  off  with  a  cloth  free 
from  lint.  The  slide  is  next  placed  in  a  drying  oven  which  is  not  warm 
enough  to  melt  the  paraffin.  It  is  well  to  let  the  slides  remain  over  night, 
but  a  few  hours  may  be  sufficient  to  dry  them  thoroughly. 

In  preparing  large  numbers  of  slides,  each  bearing  only  one  or  two  sec- 
tions, fragments  of  the  ribbon  containing  the  desired  number  of  sections 
are  floated  in  a  basin  of  water  warm  enough  to  flatten  but  not  to  melt 
them.  Slides  rubbed  with  albumen  are  dipped  into  the  water  beneath  the 
sections,  which  are  held  in  place  with  a  needle.  The  slides  are  drained 
and  dried  in  the  usual  way,  care  being  taken  to  have  the  sections  in  the 
center  of  the  slide.  Or  the  ribbons  may  be  floated  on  warm  water  and 
cut  into  fragments  with  a  heated  knife,  proceeding  then  as  before. 

To  remove  the  paraffin,  the  slides  are  immersed  in  xylol  for  about  5 
minutes.  The  slide  is  then  transferred  in  turn  to  a  mixture  of  equal  parts 
of  xylol  and  absolute  alcohol,  then  through  absolute,  95  per  cent.,  80  per 
cent.,  70  per  cent,  and  50  per  cent,  alcohols,  remaining  about  i  minute 
in  each,  to  water.  In  case  the  stain  is  in  alcoholic  solution,  the  transfers 
may  be  stopped  at  that  grade  of  alcohol  which  corresponds  to  the  solvent 
of  the  stain. 

In  case  the  sectioned  tissue  was  fixed  in  a  fluid  containing  corrosive 

sublimate  and  has  not  previously  been  treated  with  iodine  for  the  removal 

of  mercurial  deposits,  enough  tincture  of  iodine  to  give  a  port-wine  color 

may  be  added  to  the  80  per  cent,  alcohol.     The  slide  is  immersed  in  this 

32 


498  HISTOLOGY 

for  about  a  minute  and  then  washed  in  fresh  80  per  cent,  to  remove  the 
iodine. 

All  of  the  reagents  and  stains  to  be  used  for  paraffin  sections  may  be 
kept  in  a  series  of  tube-like  vials,  in  which  the  slides  may  be  placed  in 
pairs  back  to  back,  being  transferred  from  one  vial  to  another.  The  vials 
are  kept  tightly  corked,  and  the  reagents  can  be  used  for  some  time 
before  they  must  be  renewed. 

In  handling  a  large  number  of  slides,  grooved  rectangular  boxes  are  use- 
ful. Each  reagent  is  allowed  to  act,  poured  out  and  another  substituted. 

Celloidin  Sections.  Objects  imbedded  in  celloidin  are  cut  with 
either  a  sliding  or  a  precision  microtome,  the  knife  edge  meeting  the  block 
obliquely.  The  block  and  knife  are  kept  wet  with  80  per  cent,  alcohol. 
Sections  are  cut  10  to  15  //  in  thickness,  and  are  transferred,  by  means 
of  a  camel' s-hair  brush  wet  with  alcohol,  to  a  dish  of  80  per  cent,  alcohol, 
in  which  they  remain  until  wanted  for  staining. 

Celloidin  sections  are  stained  in  a  series  of  small,  shallow  staining 
dishes.  The  sections  are  taken  from  80  per  cent,  alcohol  and  transferred 
through  graded  alcohols  to  water  or  the  solvent  of  the  stain.  If  deposits 
of  corrosive  sublimate  are  present  and  were  not  removed  before  imbedding, 
the  sections  should  be  treated  as  directed  for  paraffin  sections.  The  sec- 
tions are  transferred  from  dish  to  dish  with  bent  metal  or  glass  needles. 
Celloidin  sections  are  not  treated  with  absolute  alcohol,  since  the  celloidin 
would  be  softened. 

The  handling  of  large  numbers  of  celloidin  sections  is  facilitated  if 
they  are  placed  in  a  perforated  cup  which  fits  into  another  ordinary  cup. 
The  ordinary  cups  contain  the  various  reagents  and  the  sections  are  trans- 
ferred from  one  to  another  in  the  perforated  cups.  The  latter  may  be 
obtained  as  "Hobb's  Tea  Inf users,"  and  lemonade  cups  are  of  proper 
size  to  receive  them. 

Wright's  Method  for  Frozen  Sections.  This  method  gives  permanent 
preparations  which  are  adequate  for  most  routine  purposes  in  histological 
examination,  and  saves  much  time,  labor,  skill  and  expense.  The  success 
of  the  method  depends  to  a  considerable  extent  upon  the  frozen  sections 
being  as  thin  as  good  celloidin  sections.  Special  automatic  microtomes 
may  now  be  purchased,  or  the  older  form  in  which  the  sections  are  "  chis- 
elled" from  the  block  will  give  good  results  if  properly  used. 

The  tissues  are  fixed  in  10  per  cent,  formalin  for  12  to  24  hours  or  longer. 
The  piece  is  then  trimmed  so  that  it  will  present  a  thickness  to  be  frozen 
of  not  over  5  mm.  The  other  dimensions  of  the  block  may  be  as  large 
as  the  freezing  box  of  the  microtome  will  permit.  The  block  is  rinsed  in 
water,  placed  on  the  freezing  box  with  a  few  drops  of  water  beneath  it; 
frozen  and  cut  into  sections,  which  should  not  be  over  10  or  15  /*  in 
thickness. 


FROZEN    SECTIONS  499 

The  sections  are  floated  into  water,  in  which  they  unroll.  Select  a 
good  section  and  spread  it  smoothly  on  a  slide  which  has  been  coated 
with  a  thin,  even  layer  of  albumen-glycerin.  Superfluous  water  is 
drained  off  and  the  section  pressed  upon  the  slide  with  a  piece  of  smooth 
blotting  paper,  by  exerting  an  even  but  not  great  pressure  with  the  ball 
of  the  thumb.  The  section  will  adhere  to  the  slide. 

Now  quickly  cover  the  section  with  a  small  quantity  of  95  per  cent, 
alcohol,  followed  in  a  few  seconds  by  absolute.  Pour  from  a  drop  bottle 
quickly  and  evenly  over  the  section  and  adjacent  surface  of  the  slide  a 
very  thin  solution  of  celloidin  dissolved  in  equal  parts  of  ether  and  abso- 
lute alcohol.  Drain  off  immediately,  blow  the  breath  once  or  twice  on 
the  surface  of  the  section  and  immerse  the  slide  at  once  in  water  for  a 
few  seconds.  The  thin  film  of  celloidin  thus  formed  fastens  the  section 
to  the  slide.  The  solution  of  celloidin  should  be  almost  watery  in  con- 
sistence, and  so  thin  that  it  will  form  drops  readily  without  stringing. 
If  it  is  too  thin,  it  will  not  hold  the  section  on  the  slide,  while  if  it  is  too 
thick,  the  layer  on  the  slide  will  become  white  when  it  is  immersed  in 
water.  The  film  of  celloidin  should  be  so  thin  as  to  be  almost  invisible. 

The  section  may  now  be  Stained  by  any  of  the  usual  methods  applied 
to  sections  affixed  to  the  slide.  The  thin  layer  of  celloidin  offers  no  ob- 
struction to  the  staining.  After  staining,  the  section  is  dehydrated  by 
covering  with  95  per  cent,  alcohol  for  a  few  seconds.  Absolute  is  now 
poured  on  and  allowed  to  remain  for  a  few  seconds.  This  removes  most 
of  the  celloidin,  but,  unless  the  action  is  unduly  prolonged,  the  section 
will  not  be  loosened.  Clear  in  xylol. 

The  microtomes  and  knives  mentioned  in  this  section  are  described 
and  directions  for  their  use  are  given  in  Mallory  and  Wright's  "  Patholog- 
ical Technique."  Their  use,  however,  is  seldom  learned  except  by  personal 
demonstration  in  the  laboratory. 

4.  Staining. 

The  purpose  of  staining  is  to  differentiate  the  tissue  elements.  The 
staining  of  tissues  is  in  a  measure  a  micro-chemical  color  reaction,  the 
differential  staining  being  due  to  the  fact  that  certain  elements  take  up 
more  of  the  stain  than  others. 

Stains  used  in  microscopic  work  may  be  divided  into  two  general 
classes  according  to  their  chemical  properties — (i)  basic  stains,  which* 
show  .especial  affinity  for  the  nuclei  of  cells  and  are  called  nuclear  stains, 
and  (2)  acid  stains,  which  affect  the  cytoplasm  more  readily  and  are  called 
cytoplasmic  stains.  Certain  so-called  selective  stains  (either  acid  or  basic) 
affect  one  tissue  element  especially,  or  even  exclusively.  Preparations 
may  therefore  be  stained  with  several  dyes,  each  affecting  certain  tissue 


500  HISTOLOGY 

elements  only.  Certain  stains  may  be  applied  to  the  tissue  before  it  is 
imbedded  and  sectioned.  They  are  seldom  used  except  in  the  prepara- 
tion of  embryos. 

GENERAL  STAINS. 

THE  STAINING  OF  SECTIONS. 

Haematoxylin  and  Eosin.  Haematoxylin  is  a  basic  dye  obtained  from 
logwood,  which  stains  nuclear  structures  blue.  Eosin  is  an  acid  anilin 
dye  which  stains  cytoplasm  red.  (It  is  recommended  that  all  anilin 
dyes  used  in  histological  work  be  those  prepared  by  Griibler  in  Germany.) 

There  are  many  formulae  for  the  preparation  of  haematoxylin  solutions, 
of  which  the  two  following  are  especially  useful. 

Alum  haematoxylin. 

Haematoxylin  crystals i  gm. 

Saturated  aqueous  solution  of  ammonia  alum 100  c.c. 

Water 300  c.c. 

Dissolve  the  haematoxylin  in  a  little  water  with  the  aid  of  heat,  and 
add  to  the  remainder  of  the  solution.  Put  the  mixture  in  a  bottle  and 
add  a  small  lump  of  camphor  or  thymol  to  prevent  the  growth  of  mould. 
Stopper  the  bottle  with  a  loose  plug  of  cotton  and  set  in  the  light  for  about 
10  days  to  ripen.  It  changes  to  a  deep  blue  color  during  this  process  of 
oxidation,  after  which  it  is  ready  for  use  and  is  kept  tightly  stoppered. 
It  deteriorates  and  must  be  renewed  after  a  few  months.  The  solution 
may  be  ripened  immediately  by  the  addition  of  2  c.c.  of  hydrogen  peroxide 
solution,  neutralized  by  a  crystal  of  sodium  chloride. 

For  use  after  Zenker  fixation,  the  water  in  the  above  formula  may  be 
omitted. 

Delafield's  Haematoxylin. 

Haematoxylin  crystals 4  gm. 

Alcohol,  95  per  cent 25  c.c. 

Sat.  aq.  sol.  of  ammonia  alum 400  c.c. 

The  haematoxylin  is  dissolved  in  the  alcohol  and  added  to  the  alum 
solution.  This  is  exposed  to  the  light  in  an  open  vessel  to  ripen  for  about 
4  days  and  then  is  filtered.  To  the  filtrate  is  added: 

Methyl  alcohol  (or  95  %) 100  c.c. 

Glycerin 100  c.c. 

*  This  mixture  is  exposed  to  the  light  in  a  cotton-plugged  bottle  for 
about  a  week,  after  which  it  is  again  filtered  and  tightly  stoppered.  The 
solution  keeps  for  a  considerable  time.  It  may  be  used  in  this  strength, 
but  preferably  it  is  diluted  with  one  or  two  volumes  of  water. 

Eosin  is  sold  in  two  forms,  one  soluble  in  water,  the  other  in  alcohol. 
In  connection  with  haematoxylin,  a  TV  to  i  per  cent,  aqueous  solu- 


H^EMATOXYLIN   AND    EOSIN  501 

tion  may  be  used,  but  it  is  preferable  to  use  a  solution  made  by  adding 
to  95  per  cent,  alcohol  enough  of  a  stock  solution,  consisting  of  5  gm.  of 
eosin  dissolved  in  300  c.c.  of  50  per  cent,  alcohol,  to  give  a  deep  yellowish- 
red  color  to  the  alcohol. 

Sections  are  transferred  from  water  to  the  haematoxylin  solution  for 
about  5  minutes.  They  are  then  washed  in  several  changes  of  tap  water 
until  the  sections  are  deep  blue  in  color.  If  this  change  does  not  occur 
rapidly,  a  few  drops  of  ammonium  hydrate  may  be  added  to  the  water. 
They  are  then  examined  with  the  microscope.  If  the  sections  are  over- 
stained  (a  condition  recognizable  in  the  staining  of  the  cytoplasm  as  well 
as  the  nuclei)  the  sections  are  washed  in  a  0.5  per  cent,  solution  of  hydro- 
chloric acid  in  70  per  cent,  alcohol  until  the  section  is  reddish-brown, 
usually  about  i  minute.  Wash  in  water  made  alkaline  with  a  few  drops 
of  ammonia  and  re-examine.  If  the  nuclei  are  not  well  stained,  the  sec- 
tions are  returned  to  the  haematoxylin  solution  for  5  to  10  minutes  longer, 
after  which  they  are  examined  as  before. 

When  the  stain  is  sharply  limited  to  the  nuclei  and  is  of  satisfactory 
depth,  the  sections  are  washed  for  15  to  30  minutes  in  tap  water  and  then 
are  passed  through  50  per  cent.,  70  per  cent.,  80  per  cent,  and  95  per  cent, 
alcohol,  remaining  about  i  minute  in  each.  Stain  in  the  alcoholic  solution 
of  eosin  for  i  to  5  minutes.  Wash  in  95  per  cent,  until  red  clouds  no  longer 
leave  the  section. 

Paraffin  sections  are  then  passed  through  absolute;  absolute  and  xylol 
(equal  parts) ;  and  xylol,  in  which  they  remain  for  about  5  minutes,  and 
are  then  ready  for  mounting.  Celloidin  sections  are  transferred  from 
95  per  cent,  to  oil  of  origanum  for  about  5  minutes,  before  mounting. 

Eosin  and  Methylene  Blue.  This  method  is  highly  recommended, 
especially  for  tissues  fixed  in  Zenker's  fluid  and  sectioned  in  paraffin. 

Stain  the  sections  for  20  minutes  or  longer  in  a  5  or  10  per  cent,  aqueous 
solution  of  eosin.  The  tissue  must  be  overstained,  as  the  eosin  is  partially 
extracted  in  the  subsequent  treatment.  Wash  out  the  excess  of  the  stain 
in  water. 

Stain  for  10  to  15  minutes  in  Unna's  alkaline  methylene  blue  (i  gm. 
of  methylene  blue  and  i  gm.  of  potassium  carbonate  dissolved  in  100  c.c. 
of  water)  diluted  i :  3  or  i :  5  with  water.  Wash  in  water.  Differentiate 
and  dehydrate  in  95  per  .cent,  alcohol,  keeping  the  section  in  constant 
motion  so  that  the  decolorization  is  uniform.  When  the  pink  color  re- 
turns to  the  section  and  when,  as  seen  under  the  microscope,  the  blue  is 
limited  to  the  nuclei,  the  section  is  quickly  washed  in  absolute,  passed 
through  absolute  and  xylol,  and  put  in  xylol  for  about  5  minutes. 

Heidenhain's  Iron  Haematoxylin.  The  best  results  are  obtained  with 
very  thin  paraffin  sections.  From  water  the  sections  are  transferred  to 
a  2-2.5  Per  cent,  aqueous  solution  of  ferric  ammonium  sulphate  for  4  to 


502  HISTOLOGY 

8  hours.  Wash  quickly  in  water.  Stain  for  12  to  24  hours  in  a  well- 
ripened  solution  consisting  of  0.5  gm.  haematoxylin  dissolved  in  10  c.c.  of 
absolute  alcohol  and  added  to  90  c.c.  of  water.  Wash  in  water.  Dif- 
ferentiate in  the  iron  alum  solution,  controlling  the  result  under  the  micro- 
scope. The  section  should  be  washed  in  water  before  each  examination. 
When  the  stain  is  limited  to  the  nuclei,  and  these  are  sharp,  wash  in  run- 
ning water  for  15  to  30  minutes;  50  per  cent.;  70 per  cent.;  80  per  cent.; 
95  per  cent.;  absolute  alcohol;  absolute  and  xylol;  xylol. 

If  a  counter  stain  is  desired,  add  to  95  per  cent,  alcohol  enough'  of  a 
i  per  cent,  solution  of  Orange  G  in  50  per  cent,  alcohol  to  give  a  deep 
orange  color.  Transfer  the  section  from  95  per  cent,  to  the  stain  for  a 
few  minutes.  Wash  well  in  95  per  cent.,  and  pass  through  absolute,  abso- 
lute and  xylol,  to  xylol. 

Weigerfs  Iron  Haematoxylin. 

A.  Haematoxylin  crystals i  gm. 

Alcohol,  95  per  cent 100  c.c. 

B.  Liquor  ferri  sesquichlorati 4  c.c. 

Water 95  c.c. 

Hydrochloric  acid i  c.c. 

At  the  time  of  using,  mix  equal  parts  of  A  and  B.  Transfer  the  sec- 
tions from  water  to  the  stain  for  2  to  5  minutes.  Wash  in  water.  If 
the  section  is  overstained,  add  a  few  drops  of  hydrochloric  acid  to  the 
water.  To  stop  the  decolorization,  dip  in  water  made  alkaline  with  a 
little  ammonia.  This  is  an  excellent  stain  and  gives  brilliant  results. 
If  a  counterstain  is  desired,  place  sections  for  about  i  minute  in  Van 
Gieson's  mixture: 

Picric  acid,  sat.  aq.  sol 100 

Acid  fuchsin,  i  per  cent.  aq.  sol 10 

Wash  in  water;  95  per  cent.;  absolute;  absolute  and  xylol;  xylol.  For 
celloidin  sections,  95  per  cent. ;  oil  of  origanum. 

Safranin. 

Safranin i  gm. 

Absolute  alcohol 10  c.c. 

Anilin  water 90  c.c. 

Anilin  water  is  prepared  by  shaking  up  5  c.c.  of  anilin  oil  in  95  c.c.  of 
distilled  water  and  filtering  through  a  wet  filter.  Dissolve  the  safranin 
in  the  alcohol  and  add  to  the  anilin  water. 

Safranin  is  to  be  used  after  fixation  in  Flemming's  fluid.  Stain  thin 
paraffin  sections  for  24  hours;  wash  in  water;  decolorize  in  absolute  alcohol, 
to  which  has  been  added  hydrochloric  acid  in  the  proportion  1:1000, 
until  only  the  nucleus  retains  the  stain;  fresh  absolute;  absolute  and 
xylol;  xylol. 


COCHINEAL    AND    CARMINE 


STAINING   IN  BULK. 


503 


Embryos  which  are  to  be  mounted  whole  or  cut  into  serial  sections 
are  commonly  stained  before  they  are  imbedded.  The  time  given  for 
the  action  of  the  following  stains  is  that  required  in  the  preparation  of 
i2-mm.  pigs.  Larger  or  smaller  objects  should,  of  course,  receive  a 
longer  or  shorter  treatment. 

Alum  cochineal. 

Cochineal 60  gm. 

Potassium  alum 60  gm. 

Water 800  c.c. 

Boil  vigorously  for  20  minutes.  Cool  and  filter.  Boil  the  filter 
paper  and  contents  with  more  water  for  the  same  length  of  time.  Cool 
and  filter.  Repeat  the  boiling  and  filtering  until  the  powder  disappears 
from  the  residue.  Then  put  all  of  the  filtrate  together,  boil  for  about 
20  minutes  and  make  the  volume  up  to  800  c.c. 

Stain  i2-mm.  pigs  for  about  36  hours.  Wash  in  water  for  10  to  15 
minutes;  50  per  cent,  alcohol,  20  to  30  minutes;  70  per  cent.,  i  hour;  80 
per  cent.  Imbed  in  paraffin  and  cut  in  serial  sections. 

Counterstaining  the  sections  in  the  solution  of  Orange  G  described 
with  Heidenhain's  iron  haematoxylin  will  bring  out  the  nerves  beautifully. 
The  paraffin  is  removed  in  xylol,  the  sections  passed  through  absolute 
and  xylol,  absolute,  and  95  per  cent,  to  the  stain.  Wash  in  several  changes 
of  95  per  cent.;  and  pass  back  through  absolute,  and  absolute  and  xylol, 
to  xylol. 

Borax  carmine. 

Borax 20  gm. 

Carmine 30  gm. 

Water 500  c.c. 

Boil  until  everything  is  dissolved.  Cool  and  add  500  c.c.  of  70  per 
cent,  alcohol.  Let  stand  24  hours  and  filter. 

Stain  a  i2-mm.  pig  about  36  hours;  water  10  to  15  minutes;  0.5  per 
cent,  hydrochloric  acid  in  70  per  cent.,  30  minutes  to  i  hour;  70  per  cent, 
changed  several  times,  i  hour;  80  per  cent,  changed  twice.  Imbed  in 
paraffin  and  cut  in  serial  sections.  The  sections  may  be  counterstained 
as  directed  under  alum  cochineal. 

SELECTIVE  STAINS. 
Mallory's  Phosphotungstic  Acid  Haematoxylin. 

Hsematoxylin o.  i  gm. 

Water 80.0  c.c. 

10  per  cent.  aq.  sol.  of  phosphotungstic  acid  (Merck) 20.0  c.c. 

Dissolve  the  haematoxylin  in  a  little  water  with  the  aid  of  heat;  cool, 
and  add  to  the  rest  of  the  solution.  If  the  solution  does  not  stain,  it  may 


504  HISTOLOGY 

be  ripened  by  the  addition  of  10  c.c.  of  i  per  cent.  aq.  sol.  of  potassium 
permanganate. 

Tissues  must  be  fixed  in  Zenker's  fluid.  Sections  are  transferred 
from  water  to  J  per  cent,  aqueous  solution  of  potassium  permanganate 
for  3  to  5  minutes,  washed  in  water,  and  put  for  5  to  10  minutes  in  5  per 
cent,  aqueous  solution  of  oxalic  acid.  Wash  thoroughly  in  several  changes 
of  water,  and  stain  in  the  haematoxylin  solution  for  1 2  to  24  hours.  Trans- 
fer directly  to  95  per  cent,  alcohol  for  not  more  than  i  or  2  minutes,  fol- 
lowed by  absolute  for  paraffin  sections.  Clear  in  xylol,  using  the  filter- 
paper  blotting  method  for  celloidin  sections  (see  p.  508). 

Neuroglia,  myoglia,  and  fibroglia  fibrils  and  fibrin  are  stained  blue; 
collagen  fibrils  reddish-brown;  mi  to  tic  figures  well  shown. 

Mallory's  Connective  Tissue  Stain. 

Anilin  blue  soluble  in  water  (Griibler) 0.5  gm. 

Orange  G  (Griibler) \ 2.0  gm. 

Phosphomolybdic  acid,  i  per  cent.  aq.  solution 100.0  c.c. 

Paraffin  or  celloidin  sections  of  material  fixed  in  Zenker's  fluid  are 
transferred  from  water  to  a  0.2  per  cent,  aqueous  solution  of  acid  fuchsin 
for  5  to  20  minutes.  Transfer  directly  to  the  anilin  blue  solution  and  stain 
for  20  minutes  or  longer.  Wash  in  several  changes  of  95  per  cent,  alcohol. 
Clear  celloidin  sections  in  oil  of  origanum.  Paraffin  sections  are  passed 
through  absolute,  absolute  and  xylol,  to  xylol. 

Fibrils  of  connective  and  reticular  tissue,  amyloid,  and  mucus  stain 
blue;  nuclei,  cytoplasm,  muscle,  axis  cylinders,  and  neuroglia  fibers  stain 
red;  red  corpuscles  and  myelin,  yellow. 

Weigerfs  Resorcin-fuchsin.  Boil,  in  an  evaporating  dish,  2  gm. 
of  fuchsin  and  4  gm.  of  resorcin  in  200  c.c.  of  water.  When  it  is  boiling 
briskly,  add  25  c.c.  of  liquor  ferri  sesquichlorati.  Stir  and  boil  for  5 
minutes.  Cool  and  filter.  Allow  the  precipitate  to  dry;  return  the  filter 
paper  with  precipitate  to  the  dry  dish;  add  200  c.c.  of  95  per  cent, 
alcohol  and  boil,  stirring  constantly.  Fish  out  the  paper.  Cool  and 
filter;  add  alcohol  until  the  volume  of  200  c.c.  is  reached  and  add  4  c.c. 
of  hydrochloric  acid. 

From  95  per  cent,  alcohol  the  sections,  preferably  fixed  in  alcohol  or 
formaldehyde,  are  transferred  to  the  stain  for  20  minutes  to  an  hour. 
Wash  in  95  per  cent.  Clear  in  xylol  by  the  blotting  method  (p.  508). 

The  elastic  fibers  are  stained  a  deep  purple.  The  remainder  of  the 
tissue  should  be  nearly  or  quite  colorless.  If  other  parts  are  affected,  the 
sections  should  be  washed  in  alcohol  containing  0.5  per  cent,  of  hydro- 
chloric acid.  A  light  nuclear  stain  with  alum  hasmatoxylin  after  the  elas- 
tic tissue  has  been  stained  will  increase  the  value  of  the  specimen. 

Scharlach  R.  Frozen  sections  of  fresh  or  formalin  fixed  material 
are  stained  from  15  minutes  to  over  night  in  a  saturated  solution  of  the 


SCHARLACH  505 

dye  in  70  per  cent,  alcohol.  The  sections  are  transferred  from  water  to 
the  stain,  which  has  been  freshly  filtered  into  a  tightly  closing  vessel. 
Evaporation  of  the  alcohol  causes  a  precipitation  of  the  staining  material. 
Wash  in  water,  stain  the  nuclei  lightly  with  alum  haematoxylin,  and 
mount  in  glycerin.  Fat  and  lipoids  stain  red. 

Nile  Blue.  Frozen  sections  of  fresh  material  or  material  fixed  in 
formalin  for  not  more  than  1 2  hours  are  stained  for  1 5  minutes  to  2  hours 
in  a  saturated  aqueous  solution  of  niteblue  (Griibler).  Wash  in  distilled 
water  for  5  minutes  or  more,  and  transfer  to  tap  water.  If  after  5  minutes 
in  the  tap  water  the  section  does  not  assume  a  reddish  hue,  add  a  small 
amount  of  alkali  to  the  tap  water.  When  the  section  is  reddish,  transfer 
to  distilled  water.  Mount  in  glycerin  or  glycerin  jelly  and  examine  at  once. 
Neutral  fat  red;  lipoids  blue. 

Osmic  Acid.  Fat  and  myelin  in  fresh  tissues  may  be  blackened  in  a 
i  per  cent,  aqueous  solution  of  osmic  acid.  The  myelin  sheaths  of  teased 
nerve  fibers  may  be  so  treated,  the  fragments  dehydrated,  cleared  in  chloro- 
form, and  mounted  in  chloroform  damar.  Sections  may  be  prepared  from 
tissues  fixed  in  Marchi's  fluid  (p.  491),  showing  the  fat  blackened  by  the 
osmium.  Use  chloroform  to  remove  paraffin  from  the  sections,  and 
mount  in  chloroform  damar. 

Wright's  Blood  Stain.  After  0.5  gm.  of  sodium  bicarbonate  has  been 
completely  dissolved  in  100  c.c.  of  distilled  water,  add  i  gm.  of  Griibler's 
methylene  blue  (either  the  form  called  BX,  Koch's,  or  Ehrlich's  rectified). 
"The  mixture  is  next  to  be  steamed  in  an  ordinary  steam  sterilizer  at 
1 00°  C.  for  i  hour,  counting  the  time  after  steam  is  up.  The  heating 
should  not  be  done  in  a  pressure  sterilizer,  or  in  a  water  bath,  or  in  any 
other  way  than  as  stated."  The  mixture  is  then  removed  from  the  steri- 
lizer and  allowed  to  cool,  the  flask  being  placed  in  cold  water  if  desired. 
When  cold,  it  is  poured  into  a  large  dish  or  flask.  Add  to  each  100  c.c. 
of  the  methylene  blue  solution,  stirring  or  shaking  meanwhile,  about 
500  c.c.  of  a  o.i  per  cent,  solution  of  Griibler's  yellowish  eosin  soluble  in 
water.  The  eosin  solution  should  be  added  until  the  mixture,  losing  its 
blue  color,  becomes  purple,  and  a  scum  with  yellowish  metallic  luster  forms 
on  the  surface,  "while  on  close  inspection  a  finely  granular  black  precipi- 
tate appears  in  suspension."  The  solution  is  then  filtered  and  the  pre- 
cipitate allowed  to  become  perfectly  dry  on  the  filter  paper.  The  stain 
is  made  by  dissolving  0.3  gm.  of  the  precipitate  in  100  c.c.  of  pure  methyl 
alcohol.  The  stain  need  not  be  filtered,  and  like  the  precipitate,  it  keeps 
indefinitely.  If  by  evaporation  of  the  alcohol  it  becomes  too  concentrated, 
as  shown  by  the  formation  of  a  precipitate  when  it  is  used,  it  should  be 
filtered  and  a  small  quantity  of  methyl  alcohol  added. 

Blood  is  obtained  usually  from  a  needle  puncture  in  the  lobule  of  the 
ear.  A  drop  of  blood  is  caught  in  the  center  of  a  perfectly  clean  dry 


506  HISTOLOGY 

cover,  and  another  clean  dry  cover  is  immediately  dropped  upon  it.  The 
blood  should  spread  between  the  two  cover  glasses,  forming  a  film  which 
cannot  be  too  thin.  The  covers  are  then  drawn  rapidly  apart  (they  should 
slide  along  one  another  and  not  be  lifted  apart).  The  blood  film  dries 
from  exposure  to  the  air,  and  remains  stainable  for  weeks. 

To  stain  the  blood  film,  the  cover  glass  is  to  be  held  in  cover-glass 
forceps  with  the  film  side  uppermost.  The  stain  is  applied  as  follows: 

1.  Cover  the  preparation  with  a  noted  quantity  of  the  stain  by  means 
of  a  drop-bottle  or  medicine  dropper. 

2.  After  i    minute  add  to  the  staining  fluid  on  the  preparation  the 
same  quantity  of  distilled  water,  by  means  of  the  dropper,  and  allow  the 
mixture  to  remain  i\  minutes,  not  longer.     Longer  staining  may  produce 
a  precipitate.     The  total  quantity  of  diluted  fluid  on  the  preparation 
should  not  be  so  much  that  some  runs  off.     A  metallic  scum  forms  when 
the  stain  is  properly  diluted,  but  the  stain  should  not  become  transparent. 

3.  Wash  the  preparation  in  tap  water  for  30  seconds,  or  until  the 
thinner  portions  of  the  film  become  yellow  or  pink.     Disregard  the  thick 
parts,  which  are  blue.     The  process  of  decolorizing  may  be  watched 
through  the  microscope  by  placing  the  cover  glass  with  film  side  upper- 
most on  a  slide. 

4.  Dry  and  mount  directly  in  damar. 

Silver  Nitrate.  Intercellular  cement  spaces  and  the  boundaries  of 
endothelial  cells  may  be  blackened  by  a  i  to  i  per  cent,  aqueous  solution 
of  silver  nitrate,  which  acts  chiefly  upon  free  surfaces.  The  fresh  tissue 
should  be  kept  flat,  the  mesentery,  for  example,  being  tied  over  a  detached 
bottle  neck,  while  it  is  immersed  in  the  solution  for  i  to  10  minutes. 
Transfer  to  distilled  water,  and  expose  to  direct  sunlight.  As  soon  as  it 
becomes  brown,  usually  in  5  to  10  minutes,  it  is  washed  in  0.6  per  cent, 
salt  solution.  If  desired,  the  nuclei  may  be  lightly  stained  in  alum  haema- 
toxylin.  Examine  in  glycerin,  or  dehydrate  clear  in  xyol  and  mount  in 
damar. 

Blood  vessels  may  be  injected  through  glass  tubes  with  the  silver 
solution.  Sections  are  made  and  exposed  to  the  light,  and  the  outlines 
of  the  endothelial  cells  become  dark. 

5.  Clearing  and  Mounting. 

CLEARING. 

Before  satisfactory  permanent  preparations  can  be  obtained,  the 
sections  or  object  must  be  cleared.  This  is  accomplished  by  infiltrating 
the  tissues  with  substances  which,  by  reason  of  their  high  index  of  refrac- 
tion, render  the  tissues  more  or  less  transparent.  Structures  to  be  studied 
are  previously  stained  and  thus  easily  rendered  prominent. 


CLEARING    AGENTS  507 

A  variety  of  reagents  with  widely  different  chemical  properties  are 
used.  Glycerin  and  acetate  of  potash  are  commonly  used  for  frozen 
sections  or  teased  preparations  which,  for  any  reason,  cannot  be  mounted 
in  damar. 

The  choice  of  a  clearing  agent  for  damar  mounts  depends  chiefly  on 
two  factors,  the  kind  of  stain  employed  and  the  imbedding  medium. 

Xylol.  This  is  the  best  clearing  agent  for  use  after  aniline  dyes.  It 
clears  only  from  absolute  alcohol,  through  which  celloidin  sections  cannot 
be  passed,  since  it  dissolves  celloidin.  However,  it  can  be  used  for  cel- 
loidin or  other  sections  dehydrated  in  95  per  cent,  alcohol  by  the  follow- 
ing method.  Blot  the  section  on  the  slide  with  smooth,  soft  filter  paper 
and  pour  on  a  few  drops  of  xylol.  Repeat  the  blotting,  followed  by  xylol 
two  or  three  times  and  the  section  will  be  perfectly  clear.  Paraffin  sec- 
tions attached  to  the  slides  are  cleared  by  immersion  in  a  vial  of  xylol; 
this  has  already  been  mentioned  as  the  last  step  in  the  staining  processes. 

Oleum  Origani  Cretici.  This  clears  readily  from  95  per  cent,  alcohol 
without  dissolving  celloidin  and  affects  aniline  colors  slowly.  Although 
particularly  recommended  for  clearing  after  celloidin  imbedding,  it  is 
useful  for  all  kinds  of  sections. 

Carbol-xylol. 

Carbolic  acid  crystals i 

Xylol 3 


Used  for  clearing  thick  sections  of  the  central  nervous  system  after 
carmine  and  haematoxylin  stains.  Clears  from  95  per  cent,  alcohol  with- 
out affecting  celloidin,  but  extracts  the  basic  aniline  dyes. 

Chloroform.  Since  osmic  acid  reduced  by  fat  is  soluble  in  xylol, 
chloroform  is  used  in  cases  where  permanent  mounts  of  such  preparations 
are  desired  (as  after  fixation  in  Marchi's  fluid). 

MOUNTING. 

Frozen  sections  which  cannot  be  mounted  in  damar  are  mounted 
in  glycerin,  potassium  acetate  or  glycerin  jelly. 

Glycerin  Jelly.  Soak  7  gm.  of  gelatin  for  about  2  hours  in  42  c.c. 
of  distilled  water.  Add  50  gm.  of  glycerin.  Warm,  stirring  constantly 
for  10-15  minutes.  Filter  hot  through  moistened  cotton. 

Bring  sections  on  a  slide  and  blot  off  excess  water.  Put  on  a  small 
piece  of  glycerin  jelly  and  warm  gently  until  it  melts.  Cover  and  cool. 

Preparations  mounted  in  any  of  these  three  substances  may  be 
rendered  more  or  less  permanent  by  coating  the  edges  of  the  cover  and 
adjacent  surfaces  of  the  slide  with  paraffin  or  wax. 

Gum  Damar.  Of  the  two  substances  most  commonly  employed  for 
permanent  mounts,  namely,  Canada  balsam  and  damar,  the  latter  is 
preferable,  since  balsam  turns  yellow  with  age. 


508  HISTOLOGY 

Colorless  pieces  of  damar  are  dissolved  in  xylol  and  filtered.  If 
the  solution  is  too  thin,  evaporate  to  the  proper  consistence;  if  too  thick, 
add  more  xylol.  The  proper  consistence  is  that  of  a  thin  syrup. 

A  solution  in  chloroform  should  be  prepared  in  similar  manner  for 
use  with  osmium  preparations. 

After  paraffin  sections  have  been  cleared  (3  to  5  minutes),  the  excess 
of  clearing  agent  is  drained  away  and  the  surface  of  the  slide  outside  the 
sections  is  wiped  off.  The  section  must  not  be  allowed  to  become  dry. 
A  drop  of  damar  solution  is  placed  at  once  upon  the  section  and  a  cover 
glass  is  carefully  lowered  over  it.  With  all  preparations,  whatever  the 
mounting  medium  may  be,  the  cover  glass  should  be  lowered  in  the 
following  manner.  It  is  held  over  the  specimen  and  its  left  edge  is  first 
brought  into  contact  with  the  slide;  a  needle  held  in  the  left  hand  holds 
this  edge  in  position.  Another  needle  held  in  the  right  hand  with  its 
point  beneath  the  right  edge  of  the  cover  enables  one  to  have  perfect 
control  of  the  cover  glass  while  it  is  being  lowered.  The  contact  between 
the  cover  glass  and  the  mounting  medium  spreads  gradually  from  left 
to  right  as  the  coyer  is  lowered,  expelling  the  air  as  it  advances.  If  air 
bubbles  are  caught  in  the  medium,  the  cover  may  be  alternately  raised 
and  lowered  a  little  until  they  escape,  but  once  the  cover  is  flat  upon 
the  specimen  it  should  not  be  lifted.  The  cover  glass  should  be  some- 
what larger  than  the  specimen  so  as  to  extend  beyond  it  on  all  sides. 

Celloidin  sections  which  have  been  cleared  in  oil  are  floated  over 
the  blade  of  a  spatula  placed  in  the  oil,  and  are  spread  out  flat  upon  it 
with  the  aid  of  a  needle.  They  are  then  transferred  to  a  clean  glass 
slide,  being  pulled  from  the  spatula  with  the  needle.  They  should  be 
moved  to  the  exact  center  of  the  slide,  if  the  preparations  are  to  look 
well,  and  then  the  oil  is  removed  by  placing  two  thicknesses  of  filter 
paper  over  the  section  and  pressing  upon  it  quite  firmly;  at  the  same 
time  the  section  is  made  smooth.  A  drop  of  damar  is  then  placed  upon 
the  section  before  it  dries,  and  the  cover  glass  is  applied  as  described  in 
the  preceding  paragraph. 

Damar  mounts  are  then  labelled  and  may  be  placed  in  a  drying 
oven  with  a  temperature  of  35-40°  C.  They  may  be  used  after  a  few  days, 
but  the  damar  is  not  thoroughly  hardened  for  a  considerable  time. 

SLIDES  AND  COVER  GLASSES. 

Slides  should  be  of  colorless  glass  with  ground  edges.  For  ordinary 
use,  slides  measuring  1X3  inches  (26X76  mm.)  are  preferable.  Occasion- 
ally, as  in  mounting  serial  sections,  or  large  sections  of  the  central  nervous 
system,  wider  slides  are  needed.  Thick  sliofes  are  preferable  to  thin 
ones. 


COVER    GLASSES  509 

For  ordinary  use,  cover  glasses  18-22  mm.  square  are  sufficient. 
Occasionally,  as  in  mounting  serial  sections  or  large  specimens,  oblong 
covers  may  be  needed.  If  possible,  no  covers  ranging  outside  of  0.15- 
0.18  mm.  in  thickness  (No.  i  grade)  should  be  used,  since  thicker  covers 
(No.  2  grade)  often  prevent  the  oil  immersion  lens  from  being  brought 
into  focus.  Many  valuable  sections  have  been  destroyed  in  attempting 
to  focus  through  thick  cover  glasses. 

Clean  the  slides  and  covers  by  dipping  in  alcohol  and  drying  with  a 
soft  crash  towel. or  old  linen  handkerchief.  Sometimes  it  may  be  neces- 
sary to  wash  them  in  10  per  cent,  nitric  acid,  followed  by  a  thorough 
washing  in  water  and  then  in  alcohol.  Slides  which  remain  hazy  after 
thorough  washing  must  be  discarded. 

INJECTIONS. 

The  courses  of  blood  and  lymphatic  vessels  and  of  ducts  are  studied 
by  means  of  injections.  Transparent,  deeply  colored  fluid  mixtures, 
which  will  harden  in  the  vessels,  are  used.  So-called  "warm"  injection 
masses,  which  contain  gelatin,  give  more  perfect  results  but  are  more 
difficult  to  use  than  "cold"  injection  masses. 

A  tapering  glass  or  metal  cannula  is  inserted  into  the  vessel 
or  duct,  which  is  then  tied  securely  around  it.  From  a  syringe  connected 
with  the  cannula  by  a  short  rubber  tube,  the  mass  is  then  forced  into  the 
vessel.  Pressure  may  also  be  obtained  by  having  the  injection  mass  in  a 
receptacle  which  is  connected  with  the  cannula  by  a  long  flexible  tube. 
The  pressure  is  varied  to  suit  the  needs  of  the  moment  by  raising  and 
lowering  the  receptacle. 

When  a  warm  injection  mass  is  being  used,  the  bottle  containing  the 
mass  must  be  placed  in  a  water-bath  and  kept  at  a  temperature  of  about 
45°  C.  The  organ  or  animal  to  be  injected  must  also  be  placed  in  a 
water-bath  of  the  same  temperature. 

Organs  to  be  injected  must  be  perfectly  fresh;  they  may  be  left  within 
the  body  or  removed  and  injected  separately.  It  is  advisable  to  wash 
out  blood  vessels  with  warm  salt  solution  or  Ringer's  solution  before  the 
injection. 

It  is  important  that  in  connecting  the  end  of  the  tube  carrying  the 
injection  mass  with  the  cannula  inserted  into  the  vessel,  no  air  bubbles  be 
allowed  to  enter. 

COLD  INJECTION  MASSES. 
i.  Blue  Injection  Mass. 

Soluble  Berlin  blue i 

Distilled  water. . .  20 


510  HISTOLOGY 

2.  Carmine  Injection  Mass.  Dissolve  i  gm.  of  carmine  in  i  c.c.  of 
strong  ammonia  plus  a  little  water;  dilute  with  20  c.c.  of  glycerin.  Add  i 
gm.  of  common  salt  dissolved  in  30  c.c.  of  glycerin.  To  the  whole  solu- 
tion add  an  equal  quantity  of  water. 

WARM  INJECTION  MASSES. 

1.  Berlin  Blue.    Allow  clear  sheets  of  best  French  gelatin  to  swell 
up  for  i  or  2  hours  in  double  the  quantity  of  water.     Dissolve  by  warming 
gently  over  a  water-bath  and  add,  stirring  constantly,  an  equal  volume 
of  a  warm  solution  of  Berlin  blue  prepared  as  directed  above.     Filter 
through  flannel  wrung  out  in  hot  water. 

2.  Carmine.     This  is  the  best  injection  mass  to  use,  but  it  is  very 
difficult  to  prepare.     Dissolve  2  to  4  gm.  of  the  best  carmine  in  the  re- 
quired amount  of  ammonia.     Filter  and  stir  into  10  to  50  gm.  of  a  filtered 
warm  solution  of  gelatin,  prepared  over  the  water-bath  as  described 
above.     Then  add  25  per  cent,  acetic  acid,  drop  by  drop,  stirring  con- 
stantly, until  the  mass  becomes  bright  red  and  loses  its  ammoniacal  odor. 
If  too  much  acetic  acid  is  added  a  precipitate  forms  and  the  mass  is  spoiled. 
Filter  through  warm  flannel. 

Organs  injected  with  a  cold  mass  are  put  into  80  alcohol.  After  a 
few  hours  they  may  be  cut  into  pieces.  After  injection  with  a  warm 
mass,  the  specimen  is  put  into  cold  water  to  hasten  the  solidification  of 
the  gelatin,  and  then  transferred  to  80  per  cent,  alcohol.  Imbed  in  cel- 
loidin.  Thick  sections  are  necessary  in  order  to  follow  the  course  of  the 
vessels. 

Prepared  injection  masses  for  use,  cold  or  warm,  are  sold  by  dealers 
in  microscopical  supplies. 

Many  ingenious  injection  methods  have  been  devised,  such  as  the 
injection  of  small  living  embryos  by  allowing  ink  to  enter  the  veins  and 
be  distributed  through  the  body  by  the  action  of  the  heart;  and  vessels 
have  been  injected  with  milk,  after  which  frozen  sections  were  stained 
with  Scharlach  R. 

SPECIAL  METHODS. 

The  following  special  methods  are  included  because  of  their  funda- 
mental importance.  For  the  many  other  special  methods  which  are  oc- 
casionally of  service,  reference  should  be  made  to  the  works  on  technique 
mentioned  at  the  beginning  of  this  section. 

Weigert's  Method  for  Staining  Myelin  Sheaths.  This  is  a  method  for 
the  differential  staining  of  the  myelin  sheath  of  nerve  fibers  and  is  much 
used  in  the  study  of  the  normal  and  pathological  histology  of  the  central 


nervous  system.  As  a  result  of  some  chemical  reaction  between  myelin 
and  a  chrome  salt,  the  myelin  is  fixed  so  that  it  does  not  dissolve  in  alco- 
hol and  ether,  and  at  the  same  time  is  mordanted  so  that  it  stains  deeply 
with  haematoxylin. 

1.  Fix  in  a  10  per  cent,  aqueous  solution  of  formalin  for  several  days 
to  several  weeks,  or  indefinitely.     Use  a  large  quantity  of  fluid;  change 
at  the  end  of  24  hours  and  thereafter  whenever  it  becomes  cloudy. 

2.  Cut  the  tissue  into  pieces  not  over  i  cm.  thick,  and  place  in  a  2.5 
per  cent,  aqueous  solution  of  potassium  bichromate  renewed  each  day 
for  3  or  4  days;  then  in  a  5  per  cent,  solution  renewed  each  day  for  3  to 
4  days. 

3.  Wash  in  running  water  for  24  hours  (large  pieces  severaf  days). 

4.  Transfer  the  tissues  to  the  following  solution  (Weigert's  second 
mordant)  for  24  to  48  hours. 

Acetate  of  copper 5.0  gm. 

Acetic  acid,  36  per  cent,  solution 5.0  c.c. 

Fluorchrom 2.5  gm. 

Water 100. o  c.c. 

Boil  the  fluorchrom  and  water  in  a  covered  dish;  turn  off  the  gas  and 
add  the  acetic  acid  and  then  the  acetate  of  copper.  Stir  until  the  latter 
dissolves,  and  cool. 

5.  Wash  in  running  water  24  hours  or  longer. 

6.  Dehydrate  in  graded  alcohols  and  imbed  in  celloidin.     Cut  sec- 
tions 20-25  fJ.  thick. 

7.  Stain  sections  for  12  to  24  hours  in: 

Ripened  10  per  cent,  solution  of  haematoxylin  in  absolute  alcohol 10 

Saturated  aqueous  solution  of  lithium  carbonate i 

Water 90 

The  haematoxylin  is  kept  as  a  stock  solution  and  combined  with  the 
carbonate  of  lithium  and  water  at  the  time  of  using.  Beautiful  results 
may  also  be  obtained  by  staining  over-night  or  longer  in  Weigert's  iron- 
haematoxylin  (p.  502). 

8.  Wash  in  water. 

9.  Differentiate  in  the  following  solution: 

Borax 2.0 

Potassium  ferricyanide 2.5 

Water 100.  o 

It  is  advisable  to  dilute  this  solution  with  i  or  2  volumes  of  water. 
After  the  first  staining  method,  the  gray  substance  of  the  sections  appears 
yellow;  after  the  iron-haematoxylin  it  is  colorless. 

10.  Wash  in  running  water  4  hours  to  over-night. 

11.  95  per  cent,  alcohol,  3-5  hours  (may  be  left  over-night). 

12.  Fresh  95  per  cent.,  5  minutes. 

13.  Clear  in  carbol-xylol. 

14.  Mount  in  xylol  damar. 


512  HISTOLOGY 

Pal's  Modification  of  Weigerfs  Stain.  The  tissue  is  fixed,  mordanted 
and  imbedded  as  directed  in  i,  2,  3  and  6  above.  Sections  may  be  very 
much  thicker. 

7.  Sections  are  placed  for  several  hours  in  a  J  per  cent,  aqueous  solu- 
tion of  chromic  acid,  or  for  a  longer  time  in  a  2.5  per  cent,  solution  of 
potassium  bichromate.     (May  be  omitted.) 

8.  Stain  for  24  to  48  hours  in: 

Ripened  10  per  cent,  solution  of  haematoxylin  in  absolute  alcohol 10 

Water 90 

9.  Wash  in  water  plus  i  to  3  per  cent,  of  a  saturated  aqueous  solution 
of  lithium  carbonate  until  the  sections  appear  of  a  uniform  deep  blue 
color. 

10.  Differentiate  for  20  seconds  to  i  minute  in  a  J  per  cent,  aqueous 
solution  of  potassium  permanganate. 

11.  Place  for  a  few  seconds  in  the  following  solution,  until  the  gray 
substance  is  colorless  or  nearly  so : 

Oxalic  acid i 

Potassium  sulphite i 

Water 200 

12.  Wash  in  water. 

Repeat  steps  10,  n  and  12  until  the  differentiation  is  complete.     Then 
wash  4  hours  or  longer  in  running  water. 
I3-  95  Per  cent*  alcohol,  3  to  5  hours. 

14.  Fresh  95  per  cent.,  5  minutes. 

15.  Carbol-xylol.     Mount  in  xylol  damar. 

Golgi's  Method  for  the  Impregnation  of  Nerve  Cells.  This  method 
depends  on  the  formation  of  a  fine  precipitate  in  certain  tissue  elements 
or  in  pre-existing  spaces  when  the  tissues  are  treated  with  a  solution  of 
potassium  bichromate  and  then  with  a  solution  of  silver  nitrate  or 
mercuric  bichloride.  The  value  of  the  method  lies  on  the  fact  that  it 
picks  out  here  and  there  a  cell  and  stains  it  with  its  processes  more 
or  less  completely.  This  same  fact  renders  the  method  very  uncertain. 
Of  the  several  modifications  of  this  stain,  only  one — the  so-called 
rapid  method — is  here  given. 

i .  Pieces  of  fresh  tissue  about  5  mm.  thick  are  placed  for  3  to  8  days 
in  the  following  solution: 

Osmic  acid,  i  per  cent,  solution i  part 

Bichromate  of  potassium,  3 . 5  per  cent,  solution 4  parts 

2*.  Transfer  to  a  large  quantity  of  0.75  per  cent,  solution  of  silver 
nitrate  for  2  or  3  days. 

Keep  the  tissues  in  the  dark  during  treatment  with  both  fluids. 

The  length  of  time  the  tissues  should  remain  in  the  first  solution 
depends  on  the  elements  it  is  desired  to  impregnate. 


WEIGERT'S  MYELIN  STAIN  513 

For  the  human  cord,  the  time  is  approximately  as  follows :  for  neuroglia, 
2-3  days;  nerve  cells,  3-5  days;  for  nerve  fibers  and  collaterals,  5-7  days. 

3.  Cut  sections  50  to  100  /*  thick.     They  may  be  made  free-hand  or 
with  a  microtome.     Blocks  may  be  quickly  imbedded  by  dehydrating  for 
a  few  minutes  in  absolute  alcohol,  and  placing  in  a  thick  solution  of  cel- 
loidin  for  about  5  minutes.     Harden  in  80  per  cent. 

4.  Sections  are  dehydrated  quickly  in  alcohol. 

5.  Clear  in  oil  of  cloves  or  bergamot. 

6.  Mount  without  a  cover  glass  in  xylol  damar  and  dry  quickly  at 
40°  C.     Protect  the  sections  from  the  light  and  dust  as  much  as  possible. 

If  the  method  is  unsuccessful,  the  specimens  may  be  transferred  back 
to  an  osmic  acid  and  bichromate  mixture  containing  less  osmic  acid,  and 
after  several  days  again  placed  in  the  silver  nitrate  solution  for  24  to  48 
hours. 


33 


II.  THE  EXAMINATION  OF  MICROSCOPICAL 

SPECIMENS. 

THE  MICROSCOPE. 

It  is  unfortunate  that  the  price  of  a  microscope  is  prohibitive  to 
many  medical  students,  and  that  some  who  might  purchase  instruments 
at  the  beginning  of  their  work  wait  until  later.  The  cost  is  now  so 
reduced  that  an  increasing  proportion  of  students  can  enjoy  the  advantage 
of  having  a  microscope  of  their  own. 

Microscopes  of  a  certain  grade  are  required,  and  if  they  cannot  be 
afforded,  no  instrument  should  be  bought.  The  necessary  equipment,  as 
shown  in  the  figure,  is  a  stand  with  fine  and  coarse  adjustments  ("microm- 
eter screw"  and  "rack  and  pinion"),  and  a  large  square  stage.  The 
more  expensive  round  and  mechanical  stages  are  not  necessary ^and 
since  mechanical  stages  are  detachable,  they  may  be  obtained  later  if 
desired.  There  should  be  an  Abbe  condenser  (with  iris  diaphragm),  a 
triple  revolver,  a  high  and  a  low  eyepiece  or  ocular,  and  the  following 
objectives:  a  i6-mm.  (f-inch)  and  a  4-mm.  (J-  or  i-inch)  which  must 
beparfocal;  together  with  a  2-mm.  (yV-inch)  oil  immersion,  for  cytological 
and  bacteriological  work;  and  a  48-mm.  (2-inch),  which  is  a  very  low 
power,  for  embryological  work.  The  figures  indicate  the  distance  of  the 
section  from  the  objective  when  the  specimen  is  in  focus;  the  higher  the 
power,  the  nearer  the  objective  is  brought  to  the  object.  The  2-mm. 
oil  immersion  is  an  expensive  objective,  and  its  purchase  may  be  postponed. 
The  2-inch  is  a  cheap  objective  which  is  very  useful  in  obtaining  a  view  of 
an  entire  section,  and  for  embryological  reconstructions  it  is  essential. 
It  may  be  noted  that  microscopes  are  now  being  finished  more  extensively 
in  black  enamel  than  in  lacquered  brass;  the  former  is  not  damaged  by 
alcohol  and  is  more  desirable.  Improvements  have  also  been  made  in 
the  post  and  fine  adjustment,  so  that  the  form  shown  in  the  figure,  although 
good,  is  not  the  best. 

Satisfactory  microscopes  of  American  manufacture  are  now  made, 
but  all  agree  that  the  Zeiss  microscopes  (German)  are  the  best  (and  most 
expensive).  If  the  microscope  is  purchased  by  a  student  unfamiliar 
with  its  use,  it  is  well  to  have  the  lenses  examined  by  a  disinterested 
microscopist. 

For  a  description  of  the  nature  and  use  of  the  microscope,  the  student 
is  referred  to  the  nth  edition  of  "The  Microscope,"  by  Professor  S.  H. 
Gage  (Comstock  Pub.  Co.,  Ithaca,  N.  Y.). 


THE   MICROSCOPE 


515 


For  the  sake  of  emphasis  it  may  be  said  that  the  microscopist  works 
with  his  right  hand  upon  the  fine  adjustment  and  his  left  hand  upon  the 


Eye-piece  (Ocular) 


Tube 


•  Draw-tube 


Back  and  pinion  adjustment 


Triple  revolver 
Objective  -  •  • 


•  •  Micrometer  Screw 


FIG.  493- 

slide.  As  the  latter  is  moved  about,  bringing  different  fields  into  view, 
the  focussing  is  done  with  the  adjustment  and  not  with  the  eyes.  It  is 
impossible  to  study  even  a  single  field  without  constantly  changing  the 


516  HISTOLOGY 

focus,  and  the  continuous  use  of  the  fine  adjustment  distinguishes  an 
experienced  microscopist  from  a  beginner.  Both  eyes  should  be  open 
(as  will  be  natural  after  becoming  accustomed  to  the  instrument). 
Often  one  acquires  the  habit  of  using  only  the  right  or  the  left  eye  for  micro- 
scopic work,  but  it  is  better  to  learn  to  use  both. 

Always  examine  a  specimen  first  with  a  low  power  objective  and  then 
with  a  high  power.  In  focussing  the  microscope,  have  the  objective 
drawn  away  from  the  slide  and  focus  down.  This  should  be  done  cau- 
tiously, with  a  portion  of  the  specimen  actually  beneath  the  lens;  if  there 
is  only  cover  glass  and  damar  there,  the  objective  will  probably  be  driven 
down  upon  the  slide.  Unless  one  is  sure  that  stained  tissue  is  in  the  field, 
the  slide  should  be  moved  back  and  forth  as  the  objective  is  being  lowered. 

In  working  with  the  Abbe  condenser,  the  flat  surface  of  the  mirror 
should  be  uppermost,  provided  that  it  is  used  in  daylight  and  the  rays 
falling  upon  it  are  therefore  parallel;  but  for  the  divergent  rays  of  an  arti- 
ficial light  near  at  hand,  the  concave  mirror  may  be  used,  and  the  light 
may  advantageously  be  made  to  pass  through  a  blue  glass,  which  lessens 
the  yellow  glare. 

The  objectives  must  never  be  scratched.  Lens  paper  or  fine  linen 
should  be  used  to  wipe  them.  If  they  are  soiled  with  damar  they  should 
be  wiped  with  a  cloth  moistened  with  xylol,  but  since  the  lenses  are 
mounted  in  balsam,  xylol  must  be  applied  to  them  cautiously.  A  mi- 
croscope of  the  kind  shown  in  the  figure  should  never  be  lifted  by  any 
part  above  the  stage,  lest  the  fine  adjustment  be  damaged;  the  pillar 
should  be  grasped  below  the  stage. 

RECONSTRUCTIONS  . 

There  is  an  important  arrangement  of  mirrors  (Abbe's  camera  lucida) 
for  drawing  the  outlines  of  sections.  It  is  attached  to  the  microscope 
above  the  eye-piece,  and  on  looking  into  it  one  can  see  the  image  of  the 
section  beneath  the  objective  apparently  spread  upon  the  drawing  paper 
beside  the  microscope.  Thus  the  pencil  point  can  be  seen  as  it  is  made  to 
trace  the  outline  on  the  paper.  With  a  little  practice  the  same  result 
may  be  obtained  more  or  less  perfectly  without  the  camera,  by  looking 
into  the  microscope  with  one  eye  and  at  the  same  time  upon  the  paper 
with  the  other.  This  possibility  was  noted  by  the  early  microscopists, 
and  it  is  a  useful  accomplishment.  More  satisfactory  than  the  camera 
lucida  is  the  projection  apparatus  of  Edinger,  arranged  with  an  arc  light, 
whereby  the  image  of  the  section  is  projected  through  an  inverted  micro- 
scope upon  the  drawing  paper  beneath.  With  the  camera,  or  projection 
apparatus,  a  succession  of  serial  sections  may  be  drawn  with  the  uniform 
magnification  essential  for  reconstructions.  The  magnification  is  deter- 


RECONSTRUCTIONS  517 

mined  by  substituting  a  stage  micrometer  for  the  slide  of  sections.  The 
micrometer  is  a  slide  upon  which  i  mm.,  with  subdivisions  into  twentieths 
or  hundredths,  has  been  marked  off  by  scratches  in  the  glass;  the  sub- 
divisions may  be  drawn  with  the  camera,  under  the  same  conditions  as 
the  sections,  and  the  enlargement  of  the  subdivisions  may  then  be  measured. 

From  the  camera-drawings  of  serial  sections,  wax  reconstructions  of 
various  embryonic  organs  or  small  structures  in  the  adult  can  be  built 
up.  If  the  sections  are  10  /*  thick  and  alternate  sections  have  been  drawn, 
magnified  50  diameters,  then,  on  the  scale  of  the  drawings,  these  alternate 
sections  are  i  mm.  apart.  Wax  plates  i  mm.  thick  are  therefore  to  be 
made,  either  by  rolling  beeswax,  or  by  spreading  a  weighed  amount  of 
melted  wax  in  a  pan  of  hot  water.  It  floats  and  spreads  in  an  even  layer, 
solidifying  as  the  water  cools.  The  outlines  of  the  drawings  are  then 
indented  upon  the  wax  plates,  and  the  desired  portions  are  cut  out  and 
piled  up  to  make  the  model.  In  this  way  reconstructions  like  those  of 
the  ear  (p.  466)  may  be  made.  This  method  was  first  employed  by  Born. 
Further  details  of  the  process  should  be  learned  frcm  demonstrations  in 
the  laboratory. 

Graphic  reconstructions  (first  used  by  His)  are  generally  side  views  of 
structures,  made  from  measurements  of  their  transverse  sections.  Fig. 
176,  p.  185,  is  from  such  a  reconstruction.  A  camera  drawing  of  the  side 
of  an  embryo  (or  other  structure)  is  made  before  it  is  sectioned.  The 
outline  of  this  drawing  is  enlarged,  and  parallel  lines,  equally  spaced,  are 
ruled  across  it,  corresponding  in  number  and  direction  with  the  sections 
into  which  it  was  cut.  Often  only  every  other  section,  or  every  fourth 
section,  is  used  for  the  reconstruction,  and  the  number  of  lines  to  be  ruled 
across  the  drawing  is  correspondingly  reduced.  Camera  drawings  of  a 
lateral  half  of  every  section  to  be  used  in  the  reconstruction  are  then  made, 
and  across  each  drawing  two  lines  are  ruled.  The  first  follows  the  median 
plane  of  the  body;  and  the  second  is  at  right  angles  with  it,  being  drawn 
so  as  to  touch  the  dorsal  or  ventral  surface  of  some  structure  to  be  included 
in  the  reconstruction.  Provided  that  the  camera  drawings  and  side 
view  have  been  enlarged  to  the  same  extent,  the  perpendicular  distance 
from  the  middle  of  the  back  to  the  junction  of  the  two  lines  is  marked  off 
in  the  side  view,  on  the  line  corresponding  with  the  section  in  question. 
The  perpendicular  distances  from  the  second  line  to  the  dorsal  and  to  the 
ventral  surfaces  of  all  structures  to  be  reconstructed,  are  also  marked  off 
upon  the  line  on  the  side  view.  The  same  is  done  in  the  following  sec- 
tion, and  the  points  belonging  with  a  given  structure  are  connected  from 
section  to  section.  Thus  the  outlines  of  the  organs  are  projected  upon 
the  median  plane;  two  dimensions  are  accurately  shown  but  the  third  is 
lost. 

Often  it  is  undesirable  to  attempt  to  make  the  magnification  of  the 


518  HISTOLOGY 

sections  and  of  the  side  view  identical;  the  measurements  may  be  en- 
larged or  reduced  as  they  are  transferred  for  plotting,  by  means  of  the 
draughtsman's  proportional  dividers,  an  indispensable  instrument  for 
this  method  of  reconstruction.  The  corrections  for  unequal  shrinkage 
of  the  sections  in  paraffin,  and  other  details,  can  best  be  explained  in  the 
laboratory  with  the  drawings  at  hand. 

In  addition  to  making  side  views,  this  method  may  be  used  in  recon- 
structing ventral  or  dorsal  views,  by  plotting  outward  from  the  median 
line. 

DRAWINGS. 

Since  anatomy,  both  gross  and  microscopic,  is  a  study  of  forms  and 
relations,  that  is  of  things  seen,  it  finds  natural  expression  in  drawing; 
and  the  volumes  of  wood-cuts,  copper-plates,  and  lithographs,  together  with 
the  cheaper  process-drawings  and  half-tones  of  the  present  day,  form 
almost  as  important  a  part  of  anatomical  literature  as  the  accompanying 
text.  Often  there  may  be  shown  in  a  figure  at  a  glance  what  pages  of 
writing  fail  to  make  clear;  and  it  is  significant  that  the  great  books  of 
Vesalius,  which  marked  a  new  era  in  anatomy,  were  illustrated  by  Jean 
de  Calcar,  a  pupil  of  Titian.  Burggraeve  believes  that  Vesalius  doubtless 
supplied  preliminary  sketches  and  adds — "Almost  all  the  great  anato- 
mists were  no  less  excellent  draughtsmen — Scarpa  and  Cuvier  furnish 
us  remarkable  examples — and  one  can  hardly  imagine  an  anatomist  who 
is  not  deeply  sensitive  to  the  beauty  and  harmony  of  contours  and  forms." 
Selenka  (1842-1902)  drew  the  ape  embryos,  which  he  collected  and  de- 
scribed, with  consummate  skill,  and  "  always  impressed  upon  his  students 
the  great  value  of  a  ready  pencil."  Robert  Hooke  (1635-1703)  was  far 
less  successful  with  his  drawings.  In  the  preface  to  his  fully  illustrated 
microscopical  observations,  he  makes  the  following  explanation  of  the 
defects  of  his  plates,  and  in  conclusion  sets  an  example  which  all  students 
should  follow.  He  says — 

"What  each  of  the  delineated  Subjects  are,  the  descriptions  annext 
to  each  will  inform,  of  which  I  shall  here,  only  once  for  all,  add,  that  in 
divers  of  them  the  Gravers  have  pretty  well  follow'd  my  directions  and 
draughts:  and  that  in  making  of  them,  I  indeavoured  (as  far  as  I  was  able) 
first  to  discover  the  true  appearance,  and  next  to  make  a  plain  representa- 
tion of  it." 

To  discover  the  true  appearance  of  each  section  and  to  make  a  plain 
representation  of  it,  is  by  far  the  best  method  for  beginning  the  study 
of  histology,  and  conscientious  attempts  to  represent  what  is  seen  in- 
variably lead  to  deeper  and  more  valuable  observations.  Thus  drawings 
are  unhesitatingly  required  of  all  students,  ,and  every  effort  should  be 


DRAWINGS  519 

made  to  acquire  some  skill  in  this  direction.  The  problem  of  the  micros- 
copist,  who  has  but  little  to  do  with  the  third  dimension,  is  relatively 
simple.  A  few  suggestions  may  be  given. 

Generally  sections  are  stained  in  different  colors,  and  the  question 
at  once  arises  how  to  represent  these  with  the  pencil.     The  accompanying 


FIG.  494.  DIAGRAMS  SHOWING  THE  WAY  IN  WHICH  THE  SHADE  VALUES  OF  THE  PRIMARY, 
SECONDARY  AND  TERTIARY  COLORS  MAY  BE  REPRESENTED  IN  TERMS  OF  BLACK  AND  WHITE. 
(Lee,  in  Hardesty's  "Laboratory  Guide";  Blakiston,  1908.) 

figures  indicate  the  way  in  which  this  is  done,  the  primary  colors  being 
shown  in  the  inner  ring,  and  their  combinations  in  the  outer  rings.  Red 
being  a  brighter  color  than  blue  is  to  be  made  lighter.  Orange,  a  com- 
bination of  the  two  brightest  of  the  primary  colors,  should  be  lighter  than 


520  -  HISTOLOGY 

purple — a  combination  of  the  darkest — and  lighter  than  pure  red  since 
it  has  the  brighter  yellow  mixed  with  it.  •  Thus  the  various  colors  may  be 
suggested  in  black  and  white,  and  the  contrast  between  blue  nuclei  and 
red  protoplasm  can  be  carefully  preserved  in  the  drawing.  This  is  facili- 
tated by  the  use  of  pencils  of  varying  degrees  of  hardness — "H"  and 
"3  H"  for  dark  structures,  and  "6  H"  for  pale  areas.  Soft  pencils,  whith 
rub,  should  not  be  used. 

Before  beginning  a  drawing,  the  specimen  should  be  carefully  looked 
over,  to  find  the  place  most  worthy  of  such  attention.  The  time  which 
the  drawing  is  to  take  must  be  considered,  and  a  small  area  may  be 
found  which  combines  features  elsewhere  scattered  about  the  specimen. 
The  entire  field  is  rarely,  if  ever,  to  be  drawn;  and  the  figures  should  not 
be  encumbered  with  surrounding  circles. 

The  magnification  of  the  drawing  is  next  lo  be  decided  upon.  The 
form  of  a  gastric  gland  and  the  structure  of  its  cells,  for  example,  cannot 
profitably  be  included  in  a  single  drawing.  General  features,  such  as  the 
forms  of  glands,  should  be  represented  in  "low  power"  sketches.  "Low 
power"  as  here  used  does  not  necessarily  refer  to  the  lenses  employed, 
but  means  that  the  drawing  is  on  such  a  scale  that  the  nuclei  appear  merely 
as  spots,  round  or  elongated  as  the  case  may  be.  Often,  however,  such 
a  drawing  shows  features  which  can  be  clearly  observed  only  with  high 
power  lenses.  "High-power  drawings"  are  those  which  present  details 
of  nuclear  and  protoplasmic  structure. 

Usually  in  studying  an  organ,  it  is  desirable  to  make  a  general  low- 
power  sketch  showing  the  arrangement  of  its  lobules  or  layers,  and  to 
supplement  this  by  high-power  drawings  of  the  most  significant  cells  or 
tissues.  In  these,  which  are  the  final  test  of  a  student's  keenness  of  •  ob- 
servation, no  details  of  cellular  structure  are  too  minute  for  careful  repre- 
sentation, and  "the  difficulty  of  observing  them  proves  not  the  merit  of 
overlooking  them." 

Having  selected  a  field  and  decided  upon  the  magnification,  the  out- 
lines of  the  parts  should  be  sketched  lightly,  with  a  soft  pencil,  and  cor- 
rected until  accurate.  As  finally  made,  they  should  be  definite  clean  lines, 
not  pieced  out,  representing  the  boundaries  of  layers,  nuclear  membranes, 
cell  walls  when  present,  cuticular  surfaces,  and  the  like.  Having  com- 
pleted the  outline,  shading  should  be  undertaken,  to  differentiate  substance 
from  empty  space,  and  to  indicate  the  nature  of  the  substance.  In  high- 
power  drawings  protoplasmic  texture  must  be  faithfully  reproduced — ho- 
mogeneous, finely  granular  or  coarsely  granular;  if  the  granules  are  not  dis- 
tinct enough  to  be  counted,  they  should  not  be  readily  countable  in  the 
drawing.  If  definite  walls  are  absent  from  the  specimen,  they  should 
not  be  drawn,  but  the  shaded  areas  of  the  finished  drawing  should  end 
abruptly  without  a  bounding  line. 


DRAWINGS 


Drawings  consist,  therefore,  of  two  parts — outline,  and  shaded  texture 
or  finish.  Ruskin  observes  that  the  real  refinement  of  the  outline  depends 
on  its  truly  following  the  contours,  and  in  regard  to  finish  he  offers  sug- 
gestions which  may  be  applied  to  the  drawings  of  the  wall  of  the  medullary 
tube  here  reproduced.  He  states  that  if  we  are  to  "  finish "  farther,  we 


i 


FIG.  495.    THE  WALL  OF  THE  MEDULLARY  TUBE,  AS  DRAWN  BY  Six  STUDENTS. 

must  know  more  or  see  more  about  the  object.  These  sketches  are  not 
finished  in  any  sense  but  this,  that  the  paper  has  been  covered  with  lines. 
A  piece  of  work  is  more  finished  than  others,  not  because  it  is  more  deli- 
cate or  more  skillful,  but  simply  because  it  tells  more  truth.  "  That  which 
conveys  most  information,  with  least  inaccuracy,  is  always  the  highest 
finish." 


INDEX 


Abducent  nerve,  141,  424 
Absorbents,  183 
Absorption,  intestinal,  264 
Accessory  chromosome,  23 

duct  of  pancreas,  290 

nerve,  142,  424 
Acervulus  cerebri,  438 
Acetic  acid,  488 
Acidophiles,  197 
Acinus,  58 
Acoustic  meatus,  external,  481;  internal,  477 

nerve,  141,  476 

Adamantoblasts  (ameloblasts),  103 
Addison,  on  suprarenal  glands,  405 
Adelomorphous  cells  (chief  cells},  254 
Adenoid  tissue,  207 
Adipose  tissue,  72 
Adrenalin,  406 
Aggregate  nodules,  268 
Agminated  nodules  (aggregate  nodules},  268 
Ahlfeld,  on  the  allantois,  381 
Albumen,  for  attaching  sections  to  slides,  497 
Alcohol,  for  fixation,  490 
Allantois,  245,  368,  373,  381 
Allen,  on  tubules  of  the  testis,  327 

sexual  cells,  335 

ovary,  358 
Alum  cochineal,  503 

haematoxylin,  500 
Alveolar  ducts,  301 

sacs,  302 
Alveolus,  58 

of  the  lungs,  301 

of  the  pancreas,  291 

of  the  teeth,  99 
Amakrine  cells,  446 
Ameloblasts,  103 
Amianthoid  fibers,  80 
A  mitosis,  13 
Amnion,  366,  373 
Amniotic  cavity,  367 

fluid,  370 

villi,  382 

Amceboid  motion,  n 
Amphiaster,  17 
Ampulla,  of  the  ductus  deferens,  342 

of  the  semicircular  ducts,  466 

of  the  uterine  tubes,  358 
Ampullary  nerves,  476 
Anal  canal,  273 

membrane,  247 
Anaphase,  18 

Angioblast  (angioderm)  43,  367 
Aniso tropic  substance  in  muscle,  123 
Annuli  fibrosi,  176,  178 
Anterior  neuropore,  37 
Anus,  247 
Aorta,  165 

in  young  embryos,  44 
Aortic  arches,  219 


Apdthy,  on  myofibrils,  128 

neurofibrils,  146 
Appendices  epiploicae,  273 
Appendix  epididymidis.  300,  344 

fibrosa  hepatis,  280 

testis,  327,  344 

vesiculosa,  351 

vermiformis  (processus  vermiformis) ,  270 
Aponeuroses,  77 
Aquseductus  cerebri,  422 

cochleae,  477 

vestibuli,  469 
Aqueous  humor,  442 
Arachnoid  membrane,  414,  439 

granulations,  439 
Archoplasm,  6 
Areola,  404 
Areolar  glands,  404 

tissue,  65 
Aristotle,  on  blood  vessels,  163 

generation,  365 

Arnold,  on  ovarian  follicles,  356 
Anector  pili,  386,  391 
Arteria  centralis  retinae,  440,  460 
Arteriae  helicinae,  348 
Arteries,  168 
Arterioles,  168 
Articular  cartilage,  92,  97 

discs,  98 

Aschpff,  on  the  a  trio-  ventricular  bundle,  180 
Aselli,  on  lymphatics,  182 
Association  fibers,  132 
Aster,  15 

Atretic  follicles,  358 
Atria,  of  the  heart,  175 

of  the  lungs,  302 

A  trio- ventricular  bundle  and  node,  180 
Attraction  sphere,  6 
Auditory  nerve  (acoustic  nene)  141,  476 

teeth,  473 

tube,  217,  469,  479 

vesicle,  465 

Auerbach's  plexus,  138,  248,  249 
Auricle,  469 

of  the  heart,  175 
Automatic  system,  139 
Autonomic  system,  139 
Avicenna,  on  the  intestine,  247 

hypophysis,  436 
Axial  filament,  337 
Axis  cylinder,  145 
Axolemma,  156 
Axon,  134 
Azygos  veins,  310 

B 

Badertscher,  on  eosinophiles,  198 

v.  Baer,  on  ova,  366 

Baldwin,  on  muscle  cells,  122,  124 

tendon,  127,  128 
Balsam,  507 


523 


524 


INDEX 


Bardeen,  on  the  development  of  muscle,  119 

myelin,  156 

sheath  cells  of  non-medullated  nerves,  154 
Bartholin,  on  the  ovary,  365 

suprarenal  glands,  404 

pituitary  gland,  436 

vestibular  glands  of  Bartholin,  383 
Basal  body,  7 
Basement  membrane,  53 
Basophile  cells,  69 
Begg,  on  the  vitelline  veins,  279 
Bell,  on  the  nerves,  134 
Bell,  E.  T.,  on  the  thymus,  224 
Bensley,  on  the  pancreas,  291,  294 
Berlin  blue,  for  injections,  510 
Berry,  on  intestinal  villi,  260 
Bertini,  columns  of  (renal  colums),  315 
Bichat,  on  the  nervous  system,  139 
Bicuspid  valve,  176 
Bidder,  on  bone,  92 
Bile  capillaries,  285 

ducts,  278,  288 
Bipolar  nerve  cells,  143 
Bladder.  324 

development,  245 
Blast,  67,  367 
Blood,  188 

crystals,  194 

destroying  organs,  202 

forming  organs,  202 

islands,  43 

pigments,  194 

plasma,  188 

plates  (or  platelets),  188,  199 

red  corpuscles,  188 

stains  for,  505 

vessels,  163 

white  corpuscles,  188,  195 
Blue  injection  masses,  509 
Body  cavity.  36 

stalk,  369 
Bone,  83 

blood  vessels,  96 

cartilage  replaced  by  bone,  87 

cells,  84 

compact,  87 

corpuscles,  85 

decalcification,  492 

development,  84 

endochondrial,  90 

growth,  91 

lacunae,  85 

lamellae,  92 

marrow,  202 

membrane  bones,  83 

nerves,  96 

perichondrial,  90 

spongy,  87 
Borax  carmine,  503 
Border  fibrils,  64,  114 
Bern's  method  of  reconstruction,  517 
Bourn's  fluid,  490 

Bowman,  on  the  sarcolemma,  121,  122 
Bowman's  capsule  (of  the  renal  glomeruli), 

317 

glands  (olfactory  glands},  485 
membrane  (of  the  cornea),  456 
Brachium  conjunctivum,  423,  427 
ponds,  423,  427 


Brain,  418 

cerebellum,  427 

early   development,   37;   later   develop- 
ment, 418 

hemispheres,  431 

hypophysis,  435 

medulla  oblongata,  424 

meninges,  438 

pineal  body,  437 

pons,  423 
Branchial  arches,  230 

clefts,  216,  217 

Bremer,  on  development  of  blood  vessels,  43, 
186 

pulmonary  arteries,  297 

tubules  of  the  testis,  328,  334 
Bridges,  intercellular,  53 
Bronchi,  299 
Bronchial  arteries,  297 

glands,  300 

veins,  297 
Bronchioles,  300 

respiratory,  301 

Brown,  on  pulmonary  veins,  297 
Brownian  movement,  12 
Brunner's  glands  (duodenal  glands),  259 
Brush  border,  50,  318 
Bryce  and  Teacher's  embryo,  368 
Bulbous  corpuscles,  161 
Bulbo-urethral  glands,  347 
Bulbus  analis,  247 

coli,  246 

urethrae,  348 

vestibuli,  383 

Bullard,  on  granules  in  muscle,  124 
Bundle  of  His,  180 
Burdach,  on  sympathetic  system,  139 

column  of,  412 
Bursae,  77 


Caecum,  246,  272 

cupulare,  467 

vestibulare,  467 

Cajal,  on  the  growth  of  nerves,  136 
Call-Exner  bodies,  355 
Calvert,  on  lymph  glands,  209 
Calyx,  renal,  312  . 

Camera  lucida,  516 
Canada  balsam,  507 
Canal  of  Gartner,  351 

of  Schlemm,  460 
Canaliculi,  of  bone,  85 

of  the  cornea,  458 
Canalized  fibrin,  378 
Capillaries,  164,  167 

bile,  285 

secretory,  57 

Capsula  fibrosa  hepatis,  278 
Capsule,  Bowman's,  317 

of  cartilage  cells,  78 

Glisson's,  278 

internal,  431 

of  joints,  97 

of  the  kidney,  315 

of  the  lens,  441,  452 

of  the  liver,  278 

of  the  spleen,  214 

Tenon's  (interjascial  space)  460 


INDEX 


525 


Carbol-xylol,  507 

Cardia,  251 

Cardiac  ganglion,  182 

glands,  of  the  oesophagus,  248 
of  the  stomach,  253 

muscle,  113,  128 

plexus,  138 
Cardinal  veins,  309 
Carmine,  for  injections,  510 
Carney's  mixtures,  390 
Cartilage,  77 

articular,  92,  97 

elastic,  80 

epiphyseal.  91 

nbro-cartilage,  81 

growth,  78,  79 

hyaline,  80 

Caruncula  lacrimalis,  463 
Celloidin  sections,  498 

imbedding  in,  495 
Cells,  i 

amakrine,  446 

amoeboid  motion,  n 

basket,  292,  402,  429 

basophile,  69 

centro-alveolar  (or  centro-acinal),  292 

chromaffin,  152,  406 

chief  (of  gastric  glands),  254 

Claudius's,  475 

decidual,  374 

Deiter's  (of  the  cochlea),  474 

differentiation,  9 

division,  direct,  13;  indirect,  14 

egg,  354 

eosinophmc,  69 

ependymal,  413 

epithelial,  48 

fat,  73 

form,  8 

formation,  12 

germ,  20,  334 

giant,  of  the  bone  marrow,  200,  202 

glia  (neuroglia),  64,  414,  434 

goblet,  56 

Hensen's  (in  the  cochlea),  475 

Kupffer's  (in  the  liver),  287 

lutein,  358 

mast,  69,  197 

mitral,  486 

mucous,  237 

neuroglia,  64 

olfactory,  484 

Paneth's,  262 

parietal,  255 

pigment,  71,  72 

pillar  (of  the  cochlea),  474 

plasma,  68,  70 

poly  morphonu  clear,  196 

Purkinje's,  429 

pyramidal,  431 

"resting  wandering,"  71 

Retzius's,  431 

serous,  237 

Sertoli's,  335 

sexual,  20,  334 

size,  9 

squamous,  49 

tactile,  157 

taste,  235 


Cells,  visual,  444 

vital  phenomena,  n 

wall  or  membrane,  7 
Cellulee  pneumaticae,  479 
Cement  (substantia  ossea  dentis),  99,  in 

intercellular,  10 

Central  nervous  system,  130,  409 
Centro-alveolar  cells,  292 
Centrosome,  6,  17,  33 
Cerebellum,  423,  427 
Cerebral  hemispheres,  431 

nerves;  139,  424 
Cerebro-spinal  fluid,  414 

tracts,  425 

Ceruminous  glands,  481 
Cervical  glands  (of  the  uterus),  361 

sinus,  217 

Chambers  of  the  eye,  460 
Chief  cells  (of  the  stomach),  254 
Chloroform,  507 
Choana,  481 
Chondrioconta,  63,  121 
Chondriosomes,  63 
Chondromucoid,  78 
Chorda  dorsalis,  38 
Chordae  tendinese,  176,  178 
Chordoid  tissue,  82 
Choriocapillaris,  453 
Chorioid  (coat  of  the  eye),  442,  453 

plexuses,  439 
Chorion,  366,  371,  373 

frondosum,  371,  375 

laeve,  371,  373 

vilH,  375 
Chromaffin  cells,  152,  406 

organs,  152 
Chromatin,  5 
Chromatocytes,  72 
Chromatolysis,  10 
Chromatophores,  71 
Chromosomes,  15,  19 

accessory,  23 

individuality,  20 

number,  19 
Chyle,  264 
Chyme,  264 
Cilia,  7,  50 

(eyelashes),  461 
Ciliary  arteries,  458 

body,  454 

glands,  461 

muscle,  454;  (of  Riolanus),  462 

nerves,  460 

processes,  454 
Circumanal  glands,  276 
Circumvallate  papillae  (or  vallate,)  230,  231 
Cisterna  chyli,  183 
Clark,  E.  F.,  on  amitosis,  13 

E.  R.,  on  lymphatics,  184 

J.  G.,  on  ovarian  vessels,  353 
Clarke,  column  of,  427 
Claudius's  cells,  475 
Clasmatocytes,  71 
Clearing  sections,  506 
Clitoris,  353,  383 
Cloaca,  245 
Cochlea,  471 

scala  tympani,  468 
vestibuli,  468 


526 


INDEX 


Cochlear  artery,  476 
duct,  467,  471 
nerve,  476 
Coelom,  36 

extraembryonic,  368 
Cohn,  on  ameloblasts,  103 

on  interstitial  cells  of  the  ovary,  358 
Cohnheim's  areas,  120 
Coil  glands  (sweat  glands),  398 
Collagen,  62 

Collateral  nerve  fibres,  131,  144 
Collecting  tubules,  of  the  kidney,  312,  319 
Colliculi,  422 
Colloid,  227 
Coloboma,  442 
Colon,  246,  272 
Colostrum,  402 
Column,  of  Bertini,  315 

of  Burdach,  412 

of  Clarke,  427 

of  Glisson,  274 

of  Goll,  412 

of  Morgagni,  274 

rectal,  274 

renal,  315 

spinal  cord,  411 
Commissural  fibers,  132 
Commissures  of  the  spinal  cord,  411 
Common  bile  duct,  278,  288 
Conchae,  481 

Concretions,  prostatic,  345 
Cone  cells,  445 
Conical  papillae,  230,  231 
Conjunctiva  bulbi,  443,  462 

corneae,  463 

palpebrarum,  443 

sclerae,  463 

Conklin,  on  cleavage  centrosomes,  34 
Connective  tissue,  43,  65 

cells,  67 

fibers,  65 

stains,  504 
Contour  lines,  in  dentine,  108 

in  enamel,  105 
Convoluted  tubules,  of  the  kidney,  313 

of  the  testis,  334 
Corium,  384,  385 
Cornea,  442,  456 
Corona  radiata,  356 
Coronary  ligament,  278 

sinus,  177 

sulcus,  175 
Corpora  cavernosa  clitoridis,  383 

cavernosa  penis,  348 

mammillaria,  421 

quadrigemina,  422 
Corpus  albicans,  358 

callosum,  421 

cavernosum  urethrae,  338 

haemorrhagicum,  357 

luteum,  356;  luteum  spurium,  358 

spongiosum,  326 
Corpuscles,  articular,  151 

blood,  red,  188;  white,  188,  195 

bone,  85 

bulbous  (of  Krause),  161 

colostrum,  402 

corneal,  458 

cylindrical,  161 


Corpuscles,  genital,  161 

Golgi-Mazzoni,  401 

HassalTs,  225 

lamellar,  161 

Malpighian  (renal)  315;  (splenic),  211 

nerve,  160 

Pacinian,  161 

renal,  315 

salivary,  220 

splenic,  211 

tactile  (of  Meissner),  160 

thymic,  225 

Corpuscula  amylacea,  438 
Cortex,  205 

cerebral,  431 
Corti,  organ  of,  472,  474 
Cotyledons  of  the  placenta,  379 
Councilman,  on  plasma  cells,  70 
Cover  glasses,  508 
Cowper,  on  the  stomach,  251 

glands  of,  347 
Cranial  nerves,  139,  424 
Crenated  red  corpuscles,  194 
Crescents  of  serous  cells,  237 
Crile,  on  Nissl's  bodies,  3 
Cristae  ampullares,  467 
Crypts  of  Lieberkiihn,  260 
Cumulus  oophorus,  355 
Curran,  on  the  atrio- ventricular  bundle,  180 
Gushing,  on  the  hypophysis,  435,  43  6 
Cuticula,  7,  50 

dentis,  105 
Cutis,  384 
Cuvier,  duct  of,  309 
Cylindrical  corpuscles,  161 
Cystic  duct,  288 
Cytoblastema,  12 
Cytogenetic  glands,  58 
Cytomorphosis,  9 
Cytoplasm,  2 


Dalenpatius,  on  spermatozoa,  338 

Damar,  507 

Davis,  on  spermatogenesis,  21-23,  25>  27 

Decalcification,  492 

Decidua  basalis,  371 

capsularis,  371 

reflexa,  371 

serotina,  371 

vera,  371,  373 
Decidual  cells,  374 

membranes,  366 
Decussation  of  the  lemnisci  (sensory),  426 

of  the  pyramids  (motor),  425 
Deiters,  on  nerve  cells,  145 

celle  of  cochlea,  474 
Dekhuyzen,  on  red  corpuscles,  191 
Delafield's  haematoxylin,  500 
Demilunes,  237 
Dendrite,  143 
Dental  canaliculi,  107 

cavity,  99 

fibers,  107 

groove,  102 

lamina,  100 

papilla,  101,  107 

pulp,  99,  no 

sac,  no 


INDEX 


527 


Dentine,  99,  107 

contour  lines,  108 
Dermomyotome,  41,  118 
Descartes,  on  epigenesis,  339 

pineal  body,  438 

Descemet's  membrane  (of  the  cornea),  458 
Deuteroplasm,  29 

DeWitt,  on  the  atrio- ventricular  bundle,  180 
Diaphragm,  174 
Diaphysis,  91 
Diarthrosis,  96 
Diaster,  18 

Diemerbrceck,  on  the  suprarenal  gland,  405 
Diencephalon,  421 
Digestive  tube,  245 

layers,  248 

Dilatator  muscle  of  the  pupil,  456 
Diplosome,  7 
Discus  proligerus,  355 
Dispireme,  18 
Diverticulum  ilei,  247 
Downey,  on  plasma  cells,  71 
Drawing  of  specimens,  518 
Ducts,  56 

aberrant,  of  epididymis,  330 

aberrant,  of  the  liver,  280 

alveolar,  301 

Bartholin's  (sublingual) ,  242 

cochlear,  467,  471 

common  bile,  278,  288 

Cuvier's,  309 

cystic,  288 

efferent,  329 

ejaculatory,  329,  343 

endolymphatic,  465 

Gartner's,  351 

hepatic,  288 

intercalated,  58,  240,  292 

Mullerian,  327,  349 

perilymphatic,  478 

Santorini's  (accessory  pancreatic),  290 

semicircular,  465,  470 

Stenson's  (parotid),  238 

thoracic,  183 

utriculo-saccular,  467 

Wharton's  (submaxillary) ,  242 

Wirsung's  (pancreatic),  291 

Wplffian,  306,  307 
Ductuli  efferentes,  329 
Ductus  arteriosus,  296 

deferens,  329,  342 

epididymidis,  329 

reuniens,  467 

venosus,  279 

Dujardin,  on  red  corpuscles,  191 
Duodenum,  246,  259 
Dura  mater  cerebralis,  438 

spinalis,  413 
Dyads,  24 


E 


Ear,  465 

external,  480 
internal,  470 
middle,  478 
nerves,  476 
stones,  471 
vessels.  476 


v.  Ebner,  on  enamel  prisms,  107,  108 

red  corpuscles,  191 
Ectoderm,  35,  36 

derivatives,  45 

Efferent  ducts  (of  the  testis),  339 
Egg  cells,  354 

Ejaculatory  ducts,  329,  343 
Elastic  cartilage,  80 

fibers,  66 

stain  for  elastic  tissue,  504 
Elastin,  66 
Eleidin,  388 
Embryos,  human,  earliest  stages,  366 

preservation  of,  491;  see  also  Bouin's 

fluid,  490 
Enamel,  99,  104 

organs,  100,  102 

prisms,  104 

pulp,  102 
End  bulbs  (Krause's),  161 

discs,  149 

organs  (of  Ruffini),  160 
Endocardium,  178 
Endochondrial  bone,  90 
Endolymph,  467 
Endolymphatic  duct,  465 

sac,  465,  478 
Endometrium,  360 
Endoneurium,  154 
Endoplasm,  3 
Endosteum,  91 
Endothelium,  43,  46 
Entoderm,  35,  38 

derivatives  of,  45 
Entodermal  tract,  215 
Eosin,  500 

bodies,  428 
Eosinophiles,  69,  197 
Ependyma,  409,  418 
Epicardium,  178,  181 
Epidermis,  36,  384,  386 
Epididymis,  329,  339 
Epigenesis,  339 
Epiglottis,  230 
Epineurium,  154 
Epiphysis,  of  bone,  90 
^  of  the  brain,  437 
Epithelioid  glands,  58 
Epithelium,  42,  46 

basement  membrane,  53 

bridges,  53 

cilia,  50 

columnar,  48 

cuboidal,  48 

cuticular  border,  50 

differentiation  of  cells,  50 

false,  47,  98 

glands,  54 

membrana  propria,  53 

mesenchymal,  47,  98 

neuro-epithelium,  130 

pseudo-stratified,  50 

simple,  48 

secretion,  54 

stratified,  48 

terminal  bars,  52 

transitional,  324 
Epitrichium,  384 
Eponychium,  389 


INDEX 


Epoophoron,  50 
Equational  division,  24 
Equatorial  plate,  15 
Erasistratus,  on  lymphatics,  182 
Erectile  tissue,  348 
Ehrlich,  on  mast  cells,  69 
Erythroblast,  189,  204 
Erythrocyte,  188,  202 
Eustachian  tube,  217,  469 
Eustachius,  on  lymphatics,  182 

suprarenal  gland,  404 
Evans,  on  development  of  blood  vessels,  166 

perilymphatic  blood  vessels,  188 
Exoplasm,  3 

External  acoustic  meatus,  481 
Eye,  439 

blood  vessels,  458 

chambers,  442,  460 

cornea,  442 

iris,  442,  455 

lachrymal  glands,  462,  464 

lens,  451 

lids,  461 

nerves,  460 

optic  nerve,  450 

retina,  443 

tunica  fibrosa,  456 

tunica  vasculosa,  453 

vitreous  body,  453 


Fabricius,  on  valves  of  the  veins,  164 

stomach,  251 

allantois,  373 
Facial  nerve,  141 
Falciform  ligament,  278 
Fallopian  tube,  327 
Fallopius,  on  ovarian  follicles,  365 

placenta,  372 

Farmer  and  Shove,  on  cell  division,  14,  19,  20 
Fascia,  77 

linguae,  232 

pharyngo-basilaris,  236 
Fasciculus  cerebro- spinal  is,  411,  425 

cuneatus,  412,  424 

gracilis,  412,  424 

proprius,  412 

rubro-spinalis,  425 

spino-thalamicus,  426 
Fat  cells,  73 

crystals,  74 

stains,  504 
Felix,  on  the  pronephros,  306 

Wolffian  tubules,  308 

genital  glands,  327 

paradidymis,  330 

sexual  cells,  335 
Female  genital  organs,  349 
Fenestra  cochleae,  469 

vestibuli,  469 
Fenestrated  cells,  150 

membrane,  66,  170 

Ferrein,  pyramids  of,  (in  the  kidney),  315 
Fertilization,  32 
Fiber  cells  (in  the  internal  ear),  471 

layer  of  Henle,  445 

tracts,  132  (see  also  Fasciculi). 


Fibers,  elastic,  66 

Muller's  (in  the  retina),  447 

muscle,  113,  116,  126 

nerve,  132 

osteogenic,  84 

Sharpey's  (in  bone),  92 

white,  62 
Fibrils,  in  connective  tissue  fibers,  65 

in  muscle  fibers,  113 

in  smooth  muscle,  1 14 

in  striated  muscle,  122 

in  nerve  fibers,  144 
Fibrin,  191 

canalized,  378 
Fibroblasts,  67 
Fibro-cartilage,  81 
Fibroglia,  64 

Filiform  papillae,  230,  231 
Fillets  (lemnisci),  426 
Fimbria  ovarica,  352 
Fixation  of  tissues,  489 
Flack,  on  the  sino-atrial  node,  181 
Flagella,  52 

Flemming,  on  the  origin  of  white  fibers,  63 
Flemming's  fluid,  491 
Foliate  papillae,  230,  231 
Follicles,  58 

atretic,  358 

Graafian  (vesicular  ovarian),  354 

primary  ovarian,  352 

thyreoid,  227 

Fontana,  spaces  of  (in  the  iris),  460 
Foramen  apicis  dentis,  99 

epiploicum  (of  Winslow),  280 

interventriculare  (of  Monro),  419 

interventriculare,  of  the  heart,  176 

ovale,  176 
Fore-brain,  419 
Fore-gut,  39,  245 
Formaldehyde,  491 
Formalin,  491 
Fornix,  421 

Fossa  of  Rosenmuller,  218 
Fovea  centralis,  447 
Fresh  tissues,  examination  of,  487 
Frozen  sections,  498 
Fungiform  papillae,  230,  231 
Funiculi  of  the  spinal  cord,  411 


Gartner's  duct,  351 
Gage,  on  glycogen,  78 
Galea  capitis,  336 
Galen,  on  the  intestine,  247 

stomach,  251 
Gall  bladder,  277,  289 
Ganglia,  113,  147 

cardiac,  182 

cervical,  137 

cceliac,  138 

of  the  cerebral  nerves,  141 

of  the  sympathetic  nerves  in  the  head, 
142 

retinal,  445 

spinal,  134,  147 

spiral,  476 

sympathetic,  137,  142,  150 


INDEX 


52Q 


Gastric  canal,  252 

glands,  253 
Gelatin,  62 
Genital  corpuscles,  161 

organs  (female),  349 

organs  (male),  326 

papilla,  330,  353 

ridge,  327 
Germ  cells,  20,  334 

layers,  36;  origin  of  tissues  from,  45 
Giant  cells,  of  the  bone  marrow,  200,  202 
Gill  clefts,  216,  219 
Giraldes,  organ  of,  330 
Glands,  54 

anterior  lingual,  232 

areolar,  404 

Bartholin's  (major  vestibular),  383 

Bowman's  (olfactory),  485 

bronchial,  300 

B  runner's  (duodenal),  259 

buccal,  241 

bulbo-urethral,  347 

cardiac,  248,  253 

ceruminous,  481 

cervical,  of  the  uterus,  361 

ciliary,  461 

circumanal,  276 

classification,  56,  59 

compound,  57 

Cowper's  (bulbo-urethral),  347 

cytogenic,  58 

duodenal,  259 

ducts,  56,  58 

v.  Ebner's  (serous  lingual),  238 

end-pieces,  56^ 

epithelial,  54 

epithelioid,  58 

fundus  (gastric),  253 

gastric,  253 

intestinal,  259,  260 

labial,  241 

lachrymal,  462,  464 

Lieberkiihn's  (intestinal),  259,  260 

lingual,  241 

LittrS's  (urethral),  347 

lumen,  57 

lymph,  205 

mammary,  401 

Meibomian  (tarsal),  462 

mixed,  241 

molar,  241 

Moll's  (ciliary),  461 

Montgomery's  (areolar),  404 

mucous,  54,  241 

cesophageal,  248 

olfactory,  485 

oral,  237 

palatine,  241 

peptic  (gastric),  253 

praeputial,  398 

pyloric,  256 

sebaceous,  237,  397 

secretory  capillaries,  57 

serous,  54,  238 

simple,  57 

sublingual,  242 

submaxillary,  242 

sudoriparous,  398 

suprarenal,  404 

34 


Glands,  sweat,  398 

tarsal,  462 

tracheal,  299 

Tyson's,  398 

unicellular,  56 

urethral,  326,  347 

vestibular,  383 
Glans  penis,  330 

Glia  cells  (neuroglia),  64,  414,  434 
Glisson's  capsule,  278 

columns,  274 
Glomerulus,  307 

of  the  kidney,  313 

of  olfactory  nerves,  486 

of  Wolflian  body,  307 
Glomus  caroticum,  229 
Glossopharyngeal  nerve,  142,  424 
Glycerin  jelly,  507 
Glycogen,  78 
Goblet  cells,  56 
Golgi  preparations,  145 

method,  512 

Golgi-Mazzoni  corpuscles,  401 
Goll,  column  of,  412 
Gower's  tract,  427 
Graafian  follicles,  356,  365 
Granules,  in  protoplasm,  3 

metachromatic,  70 
Grasshopper,  sex  determination,  28 

spermatogenesis,  21 
Gray  matter  (substance),  416 

nerves,  153 

rami,  137 

Gr6goire  and  Wygaerts,  on  cell  division   15 
Gregor,  on  muscle  spindles,  127 
Grosser,  on  pharyngeal  pouches,  219 

yolk-sac,  368 
Gubernaculum  testis,  331 
Gum  damar,  507 
Gums  (gingiva),  112 
Gustatory  organ  (taste-buds),  232,  234 


Haematoidin,  194 
Haematoxylin,  500 
Hsemin,  194 
Haemoglobin,  188,  194 
Haemolymph  glands,  200 
Haemolysis,  195 
Hasmosiderin,  194 
Hair,  389 

bulb,  389 

lanugo,  391 

papilla,  389 

root,  389,  391 

shaft,  394 

shedding,  396 

Hair-cells,  of  the  cochlea,  471,  474 
Halban,  on  muscle  fibers,  126 
Hale,  on  the  allantois,  373 
Haller,  on  epithelium,  46 

thymus,  222 
Hammar,  on  pharyngeal  pouches,  218 

thymus,  222,  225 
Hardesty,  on  nervous  tissue,  415 

inembrana  tectoria,  473 
Harrison,  on  the  growth  of  nerves,  135,  146 
Harvey,  on  epigenesis,  339 


530 


INDEX 


Harvey,  R.  W.,  on  epithelium  of  the  bladder, 

324 

Hassall's  corpuscles  (thymic),  225 
Haustra,  273 
Haversian  systems,  94 
Head-bend,  419 
Heart,  174 

endocardium,  178 

epicardium,  178,  181 

myocardium,  178,  179 

nerves,  181 

pericardium,  178 

valves,  176 

Hedblom,  on  uterine  glands,  361 
Heidenhain,  on  muscle  contraction,  124 

intercalated  discs,  129 
Heidenhain's  iron  haematoxylin,  501 
Hemiazygos  veins,  310 
Hemispheres,  cerebral,  431 
Henle,  on  collagenous  fibers,  62 

transitional  epithelium,  324 

aberrant  ducts,  330 
Henle's  fiber  layer  of  the  retina,  445 

layer  of  the  hair  sheath,  394 

loops  in  the  kidney,  313 

spindle  cell  layer  in  the  iris,  456 
Hensen,  on  the  number  of  ova,  29 

ovulation,  357 
Hensen's  cells  of  the  cochlea,  475 

membrane  in  striated  muscle,  123 
Hepatic  arteries,  280 

cells,  284 

diverticulum,  276 

duct,  277,  288 

lobules,  281 

trabeculae,  277 

veins,  277,  282 
Hertwig,  on  mesenchyma,  59 

origin  of  nerves,  132 
Hertzog's  embryo,  368 
Hewson,  on  the  thymus,  222 
Hilus,  205 
Hind-brain,  422 
Hind-gut,  39,  245 
Hippocrates,  on  the  intestine,  247 
His,  on  endothelia,  46 

development  of  nerves,  136 

allantois,  373 

Hochstetter,  on  the  cardinal  veins,  310 
Home,  on  the  stomach,  251 
Hooke,  on  cells,  8 

drawing,  518 

Horns  of  the  spinal  cord  (columns),  411 
Houston's  valves,  273 
Howship's  lacunae,  86 
Howell,  on  red  corpuscles,  191 

white  corpuscles,  195 
Huber,  on  the  notochord,  38 

end-discs,  149 

tubules  of  the  kidney,  314,  318 

tubules  of  the  testis,  334 

ceruminous  glands,  481 
Hubrecht,  on  the  trophoblast,  367 
Huntington,  on  lymphatics,  186 

bronchi,  296 

supracardinal  vein,  310 
Huschke's  auditory  teeth,  473 
Huxley,  on  the  cuticula  dentis,'  105 
Huxley's  layer  of  the  hair  sheath,  394 


Hyaline  cartilage,  80 
Hyaloid  artery,  442 

canal,  442 

membrane,  453 
Hyaloplasm,  4 
Hydatid  of  Morgagni,  344 

sessile,  344 

stalked,  344 
Hymen,  350 
Hypogastric  plexus,  139 
Hypoglossal  nerve,  142,  424 

nucleus,  426 
Hypophysis,  435 
Hypospadias,  330 
Hypothalamus,  421 
Hyrtl,  on  the  intestine,  247 

amnion,  373 

meninges,  413 

pituitary  gland,  436 

I 

Idiozome,  336 

Ileo-caecal  valve  (valve  of  the  colon),  261 

Ileum,  246,  260 

Imbedding,  493,  495 

Implantation  of  the  ovum,  370 

Incisures  of  Lantermann  (in  myelin  sheaths) 

155 

Inclusions,  5 
Incus,  469 
Infundibulum  of  the  fore-brain,  421 

of  the  lungs,  302 

of  the  uterine  tubes,  358 
Injections,  509 
Inner  cell  mass,  35 
Intercalated  discs,  129 

ducts,  58,  240,  292 
Intercellular  bridges,  53 

secretory  capillaries,  57 

substance,  10 
Interfascial  space,  460 
Interglobular  spaces  in  dentine,  no 
Intermediate  nerve,  141 
Internal  acoustic  meatus,  477 

secretions,  58 
Interstitial  cells  of  the  ovary,  358 

cells  of  the  testis,  332 

granules  in  sarcoplasm,  124 
'lamellae  of  bone,  94 
Interventricular  foramen,  of  the  heart,  176 

of  the  brain  (Monro),  419 
Intestinal  absorption,  264 

glands,  259,  260 

villi,  260 
Intestine,  large,  270 

small,  246 

Intracellular  secretory  canals,  57 
Involuntary  muscle,  113,  128 
Iris,  442,  455 

Iron  hsematoxylin,  501,  502 
Islands  of  Langerhans,  292 
Isolation  of  tissues,  488 
Iso tropic  substance  in  muscle,  123 
Isthmus,  422 


Jacobson's  organ  (vomero -nasal  organ),  141, 
483 


INDEX 


531 


Jejunum,  246,  260 

Johnson,  on  the  rectum,  247,  273 

intestinal  villi,  260,  272 

distention  of  the  small  intestine,  262 
Johnston,  on  the  nervus  terminalis,  141 
Joints,  96 
Jordan,  on  intercalated  discs,  129 


Karyokinesis,  14 
Karyolysis,  10 
Karyoplasm,  2 
Karyorrhexis,  10 

Keibel,  on  the  development  of  the  urogenital 
tract,  350 

allantois,  368 

Keith  and  Flack,  on  the  sino-atrial  node,  181 
Kent,  on  the  atrio- ventricular  bundle,  180 
Keratohyalin,  388 

Kerkring's  valvulae  conniventes,  261 
Kidney,  310 

calyces,  312 

capsule,  315 

columns,  315 

corpuscles,  315 

cortex,  315 

labyrinth  (pars  convoluta),  315 

lobes,  321 

medulla,  315 

medullary  rays  (pars  radiata\  315 

pelvis,  311,  322 

pyramids,  314 

vessels  and  nerves,  321,  322 

zones  of  the  medulla,  316 
Kiernan,  on  the  portal  canals,  282 
Kingsbury,  on  mitochondria,  4 
Kingsley,  on  the  pineal  body,  438 
Kling,  on  lymph  glands,  205 
Kolliker,  on  osteoclasts,  86 

growth  of  bone,  91 

aorta,  172 

paradidymis,  330 
v.  Korff,  on  dentinal  fibers,  108 
Krause's  corpuscles,  bulbous  and  cylindrical, 
161 

membrane  in  striated  muscle,  123 
Kupffer's  stellate  endothelial  cells,  287   ^ 


Labia  majora,  353,  383 

minora,  353,  383 
Labium  tympanicum,  473 

vestibulare,  473 
Labra  glenoidalia,  98 
Labyrinth,  of  the  ear,  469 

of  the  kidney  (pars  convoluta),  315 
Lachrymal  glands,  464;  accessory,  462 

sac,  464 

Lacteals,  201,  267 
Lactiferous  sinus,  404 
Lacunae,  of  bone,  85 

of  cartilage,  78 

Howship's,  86 

urethral,  347 
Lamellae  of  bone,  92 
Lamellar  corpuscles,  161 


Lamina  choriocapillaris,  453 

cribrosa,  451 

fusca,  453 

spiralis,  471 

suprachorioidea,  453 
Langer,  on  lymphatics,  186 
Langerhans,  cells  of  in  epidermis,  159 

islands  of,  292 
Lantermann's  incisures,  155 
Lanugo,  391 
Large  intestine,  270 
Larynx,  298 
Leeuwenhoek,  on  the  teeth,  105 

red  corpuscles,  191 

spermatozoa,  338 
Lens,  439,  451 
Lentic  vesicle,  439 
Lesser  omentum,  278 
Leucocytes,  188,  195,  199 
Lewis,  F.  T.,  on  lymphatics,  185 

shape  of  red  corpuscles,  191 

stomach,  252 

vena  cava,  280 

ventral  pancreas,  290 

amniotic  villi,  383 
Lewis,  W.  H.,  on  muscle,  118 

development  of  the  lens,  440 
Lewis,  W.  H.  and  M.  R.,  on  the  growth  of 

nerve  fibers,  146 
Lieberkuhn,  crypts  of  (intestinal  glands)  259, 

260 
Ligaments,  77,  97 

denticulate,  414 

hepatic,  278 

ovarian,  352 

pectinate,  458 

suspensory,  of  lens,  449 
Ligamentum  spirale,  471 
Limbus  spiralis,  472 
Lingual  glands,  232,  241 

tonsil,  218,  222 
Linin,  5 
Lips,  235 
Liquor  ammi,  370 

folliculi,  355 

Littre",  glands  of  (urethral  glands),  347 
Liver,  276 

artery,  280 

bile  capillaries,  285 

capsule,  278 

ducts,  288 

hepatic  cells,  284 

ligaments,  278 

lobes,  280 

lobules,  281,  284 

peri  vascular  tissue,  286 

portal  canals,  282,  287 

structural  units,  284 

veins,  278 

Lode,  on  the  number  of  spermatozoa,  29 
Loeb,  on  fertilization,  34 
Long,  on  maturation,  31,  32 
Lowsley,  on  the  prostate,  345 
Lumen  of  glands,  57 
Lungs,  301 

alveoli,  301 

atria,  302 

development,  295 

lobules,  304 


532 


INDEX 


Lungs,  pigment,  304 

pleura,  296,  304 

structural  units,  304 

vessels  and  nerves,  303,  304 
Lunula,  389 
Lutein  cells,  358 
Lymph,  201 

follicles  (nodules),  204,  205 

glands,  204 

nodes  (lymph  glands),  204 

nodules,  solitary,  207;  aggregate,  207 

sacs,  185 

sinuses,  205,  208 
Lymphatic  vessels,  182 

development,  183,  185 

stomata,  270 

valves,  1 88 

Lymphocytes,  70,  196,  202 
Lymphoid  tissue,  207 


M 


MacCallum,  on  lymphatics,  184 

Wolffian  bodies,  309 
McClung,  on  spermatpgenesis,  21,  23 
McClure,  on  lymphatics,  186 

supracardinal  vein,  310 
McCotter,  on  the  nervus  terminalis,  141 
McGill,  on  smooth  muscle,  114,  u6,vii8 
Macula  acustica,  467 

lutea,  447 

Magma  reticulare,  368 
Mall,  on  reticular  tissue,  61 

cartilage,  77 

endocardia!  connective  tissue,  178 

spleen,  212 

lobules  of  the  liver,  281 
Malleus,  469 
Mallory,  on  fibroglia,  64 
Mallory's  connective  tissue  stain,  504 

phospho-tungstic  acid  haematoxylin,  503 
Malpighi,  on  capillaries,  164 

lobules  of  the  liver,  281 

skin,  386 

Malpighian  corpuscles  (renal),  315;  (splenic), 
211 

pyramids,  314 
Mammillary  bodies,  421 
Mammary  glands,  401 
Marchi's  fluid,  491 
Mark,  on  maturation,  31,  32 
Marrow,  202 

Mascagni,  on  lymphatics,  183 
Mast  cells,  69,  197 
Maturation,  20 

Maurer,  on  capillaries  in  epithelium,  53 
Maximow,  on  the  centrosome  in  amitosis,  13 

mast  cells,  69 

clasmatocytes,  71 

lymphocytes,  195 
Meek  el,  on  the  thymus,  222 
Meckel's  diverticulum,  247 
Meconium,  272 
Mediastinum,  of  the  testis,  328 

of  the  thorax,  295 
Medulla,  205 

oblongata,  424 

ossium,  202 

spinalis,  409 


Medullary  groove,  36 

tube,  36,  409 

Medullated  nerve  fibers,  144 
Megakaryocytes,  202 
Megaloblasts,  189 

Meibomian  glands  (tarsal  glands'),  462 
Meigs,  on  the  contraction  of  smooth  muscle, 

II7. 
contraction  of  striated  muscle,  124 

Meissner's  corpuscles,  tactile,  160 

plexus,  269 
Melanin,  72 
Membrana  basilaris  (of  the  cochlea),  473 

limitans  externa  (of  the  retina),  444 

limitans  interna,  446 

propria,  53 

vestibularis  (of  the  cochlea),  471 
Membrane,  Bowman's  (of  the  cornea),  456 

Descemet's  (of  the  cornea),  458 

hyaloid,  453 

pupillary,  451 

Reissner's  (membrana  vestibularis),  471 

tympanic,  469,  480 
Meninges,  413,  438 
Menstruation,  363 

Merkel,  on  the  origin  of  white  fibers,  63 
Mesencephalon,  421 
Mesenchyma,  59 
Mesenchymal  epithelium,  47,  98 

tissues,  59 
Mesentery,  269 
Mesoderm,  35,  39 

derivatives,  45 
Mesodermic  somites,  39,  118 
Mesonephros  (Wolffian  body),  307 
Mesothelium,  47 
Mesovarium,  353 
Metachromatic  granules,  70 
Metaphase,  17 
Metencephalon,  423 
Methylene  blue,  501 
Meves,  on  the  origin  of  white  fibers,  63 

fibroglia,  114 

spermatozoa,  337 
Micron,  9 
Microscope,  514 
Microtome,  496 
Mid-brain,  421 
Milk,  403 
Miller,  on  peri  vascular  lymphatics,  188 

pulmonary  arteries,  297 

lungs,  302 

Mingazzini,  on  intestinal  absorption,  264 
Minot,  on  cytomorphosis,  9 

mesothelium,  47 

sinusoids,  166 

blood  corpuscles,  195 

trophoderm,  367 
Miram,  on  Paneth's  cells,  263 
Mitochondria,  4,  54,  63,  239 
Mitosis,  14 
Mitral  cells,  486 

valve,  176 
Mixed  glands,  241 
Modiolus,  467 

Moenkhaus,  on  fertilization,  34 
Moll,  glands  of  (ciliary  glands),  461 
Mononuclear  leucocytes,  196 
Monophyletic  theory  of  blood  formation,  195 


INDEX 


533 


Monro,  foramen  of,  419 

Montgomery's  glands  (areolar  glands},  404 

Morgagni,  hydatid  of  (appendix  testis),  327, 

344 

sinus  of  (ventricles  oj  the  larynx},  298 
Morpurgo,  on  muscle  fibers,  126 
Morula,  35 
Motor  cells,  132,  134 

endings,  163 

nerves,  134 

plate,  163 

Mounting  sections,  507 
Mouth,  215 
Mucins,  62 
Mucous  bursae,  77 

glands,  54,  241 

tissue,  62 
Mucus,  62 

M  tiller,  on  the  Wolffian  bodies,  327 
Miillerian  duct,  327,  349 
M  tiller's  fibers,  of  the  retina,  447 
Multipolar  ganglion  cells,  143 
Muscle,  113 

cardiac,  113,  128 

columns,  120 

contraction,  117,  124 

fibrils,  113,  114,  1 20 

involuntary,  113 

skeletal,  118 

smooth,  113 

spindles,  127,  159 

striated,  113,  122,  125,  128 

voluntary,  113      ^> 
Myelencephalon,  424 
Myelin,  144,  155 
Myelocytes,  202,  203 
Myenteric  plexus,  138,  248,  269 
Myoblasts,  114 
Myocardium,  178,  179 
Myofibrils,  113 
Myoglia,  64 
Myometrium,  360 
Myotome,  118 

N 

Naboth,  ovules  of,  361 
Nagel  on  oogenesis,  30 
Nails,  389 
Nares,  481 
Nasal  pits,  481 

septum,  481 

Nasolachrymal  ducts,  465 
Nasmyth's  membrane  (cuticula  dentis),  105 
Neck-bend,  419 
NSmec,  on  mitosis,  14,  18,  19 
Nephrotome,  41 
Nerve  cells,  130,  132 

bipolar,  143 

dendrites,  143 

multipolar,  143 

neuraxon,  134,  143 

in  spinal  ganglia,  134 

in  sympathetic  ganglia,  150 

unipolar,  143 
Nerve  corpuscles,  160 
Nerve  endings,  free,  157 

motor,  163 

sensory,  157 

tactile  menisci,  158 


Nerve  fibers,  132 

afferent,  132,  134 

association,  132 

axis  cylinders,  145 

axolemma,  156 

collateral,  134,  144 

commissural,  132 

efferent,  132,  134 

growth,  135 

incisures,  155 

motor,  132 

neuraxon,  134,  143 

neurofibrils,  144 

neurolemma,  144 

neuroplasm,  156 

nodes  of  Ranvier,  144   156 

reflex  path,  131 

Remak's  fibers,  145 

sensory,  132 

sheath  of  Schwann,  144 

in  the  spinal  cord,  415 

structure,  153 
Nerves,  153 

automatic,  139 

autonomic,  139 

cerebral,  139 

gray,  153 

medullated,  154 

non-medullated,  153 

spinal,  133 

sympathetic,  137 

visceral,  139 

white,  153 
Nervous  system,  130 

central,  130,  409 

peripheral,  130 

sympathetic,  137,  139 
Nervus  terminalis,  141,  483 
Neumann's  sheath,  109 
Neural  crest,  133 

tube  (medullary  tube),  36 
Neuraxon,  134,  143 
Neuroblasts,  134 
Neuro-epithelial  cells,  130 
Neurofibrils,  144 
Neuroglia,  64,  114,  434,  451 
Neurokeratin,  155 
Neurolemma,  144 
Neurone,  145 
Neuroplasm,  156 
Neuropores,  37 
Neutrophiles,  199 
Nile  blue,  505 
Nissl's  bodies,  3,  416 
Nitric  acid,  489 
Nodes  of  Ranvier,  144,  156 
Nodules,  aggregate,  207,  268 

solitary,  207 
Nodulus  thymicus,  218 
Non-medullated  nerves,  153 
Normoblasts,  189 
Nose,  481 
Notochord,  38,  83 
Notochordal  tissue,  82 
Nuclear  membrane,  5 

sap,  5 

Nucleolus,  6 
Nucleus,  ambiguus  426 
of  cells,  5 


534 


INDEX 


Nucleus  cuneatus,  426 

dorsal,  417,  427' 

gracilis,  426 

of  the  nervous  system,  417 

pulposus,  38 

pycnotic,  10,189 
Nuel's  spaces,  475 
Nussbaum,  on  sexual  cells,  335 
Nutrient  artery,  96 


Oculomotor  nerve,  141,  422 

Odontoblasts,  107 

Odoriferous  glands,  399 

(Esophagus,  246,  248 

Oil  of  origanum,  507 

Oken,  on  the  Wolman  bodies,  326 

Olfactory  bulb,  421 

cells,  483 

epithelium,  483 

glands,  485 

nerves,  141,  486 
Olive,  424 
Oocytes,  28,  354- 
Oogenesis,  20,  28 
Oogonia,  28 

Opie,  on  the  islands  of  the  pancreas,  295 
Optic  cup,  440 

nerve,  141,  449 

recess,  419 

stalk,  439 

vesicle,  439 
Ora  serrata,  442,  449 
Oral  plate,  215 
Organ  of  Corti  (spiral  organ),  472,  474 

of  Rosenmiiller  (epoophoron),  350 

of  Zuckerkandl,  152 
Organs,  46 
Orth's  fluid,  491 
Osmic  acid,  505 
Ossification,  90 
Osteoblast,  84 
Osteoclast,^ 
Osteo-dentine,  no 
Osteogenic  fibers,  84 
Otoconia,  476 
Otocyst,  465 
Otoliths,  471 
Ova,  discovery  of,  365 

maturation,  31 

mature,  28 

number  in  human  female,  29 
Oviduct,  365 
Ovulation,  31,  356 
Ovules  of  Naboth,  361 
Oxyhsemoglobin,  194 
Oxyphiles,  197 


Pacchionian  bodies  (arachnoid  granulations), 

439 

Pacinian  corpuscles  (lamellar  corpuscles'),  161 
Palate  processes,  481 
Palatine  glands,  241 
tonsils,  218,  219 
Pallium,  420 
Palpebrae,  461 


Pal's  modification  of  Weigert's  stain,  512 
Pancreas,  289 

centro-alveolar  cells,  292 

dorsal,  289 

islands,  292 

ventral,  289 
Paneth,  cells  of,  262 
Panniculus  adiposus,  386 
Papilla,  duodenal,  259,  278 

genital,  330 

of  hair,  389 

of  the  optic  nerve,  441 

renal,  314 
Papillae,  of  the  corium,  385 

of  the  tongue,  230- 
Paradidymis,  330,  344 
Paraffin,  imbedding  in,  493 

sections,  496 
Paraganglia,  152 
Parametrium,  363 
Paranucleus,  26 
Parathyreoid  glands,  218,  228 
Parenchyma,  46 

of  the  liver,  284 
Parietal  cells,  255 
Parker,  on  cilia.  52 

on  the  nervous  system,  132 
Paroophoron,  350,  351 
Parotid  gland,  238 
Parovarium  (epoophoron),  350 
Pavement  epithelium,  48 
Pecquet,  on  lymphatics,  183 
Pectinate  ligament,  458 
Peduncles  of  the  cerebrum,  422 
Pelvis  of  the  kidney,  311,  322 
Penicilli,  212 
Penis,  346 

Peptic  glands  (gastric  glands),  253 
Perforating  fibers,  of  Sharpey,  92 
Perforatorium,  336 
Pericardial  cavity,  174 
Pericardium,  178 
Perichondrial  bone,  90 
Perichondrium,  79 
Periodontal  membrane,  (alveolar  periosteum), 

in 

Perilymph,  468 
Perilymphatic  duct,  478 
Perimetrium,  360 
Perimysium,  124 
Perineum,  247 
Perineurium,  154 
Peripheral  nerves,  syncytial  interpretation  of, 

145 

Peripheral  nervous  system,  130 
Periostea!  lamellae,  93 
Periosteum,  91,  92 
Peritoneum,  269 
Permanent  preparations,  489 
Peter,  on  the  zones  of  the  renal  medulla,  316 
Peters 's  embryo,  368 
Petit,  canal  of  (zonular  spaces),  449 
Peyer's  patches  (aggregate  nodules),  207,  268 
Pfl tiger's  egg  tubes,  352 
Phagocytes,  12,  197 
Pharyngeal  pouches,  216,  217 

recess,  218 

tonsil,  218,  222 
Pharynx,  215 


INDEX 


535 


Phospho-tungstic  acid  haematoxylin,  503 

Pia  mater,  413,  439 

Pigment  cells,  71,  72 

Pillar  cells  of  spiral  organ,  474 

Pineal  body,  421,  437 

Pinguecula,  462 

Pinkus,  on  the  nervus  terminalis,  141 

on  the  skin,  388 
Pinna,  469 

Pituitary  gland  (hypophysis),  436 
Placenta,  372,  375 

succenturiate,  372 
Plasma,  188,  201 
Plasma  cells,  68,  70 
Plates,  blood,  188,  199 
Pleura,  296,  304 
Pleural  villi,  306 
Plexus  annularis,  461 

Auerbach's,  138,  248,  269 

cardiac,  138 

chorioid,  439 

cceliac,  138 

gangliosus  ciliaris,  461 

hypogastric,  139 

Meissner's,  269 

myenteric,  138,  248,  269 

pulmonary,  304 

solar,  139 

submucous,  139,  248,  269 
Plica  semilunaris  of  the  eyelid,  463 
Plicae  adiposae,  of  the  pleura,  306 

circulares,  of  the  small  intestine,  260,  261 

palmatae,  of  the  uterus,  360 

semilunares,  of  the- large  intestine,  273 

transversales,  of  the  rectum,  273 

villosae,  of  the  stomach,  252 
Polar  bodies,  31 

field,  20 

radiations,  17 
Polykaryocyte,  202 
Polymorphonu clear  leucocytes,  196 
Polyphyletic  theory  of  blood  formation,  195 
Pons,  423 
Porta  hepatis,  279 
Portal  canals,  282,  287 

lobules,  284 

vein,  277,  278 
Potassium  chlorate,  489 

hydrate,  489 
Praeputial  glands,  398 
Praespermatid,  22 
Praespermid,  22 
Precartilage,  77 
Predentine,  107 
Preformation  theory,  339 
Premyelocytes,  202,  203 
Prenant,  on  amianthoid  fibers,  80 
Prepuce,  33 /,  398 
Primitive  knot,  35 

streak,  35 

Prisms,  enamel,  104 
Processus  vaglnalis,  331 

vermiformis,  270 
Pronephros,  306 
Pronucteas,  32 
Prosencephalon,  419 
Prostate,  345 
Prostatic  utricle,  327 
Protoplasm,  2 


Protoplasmic  processes,  145 
Protovertebrae  (mesodermic  somites),  39,  118 
Prowazek,  on  cilia,  51 
Pseudopodia,  7  • 
Pseudostratified  epithelium,  50 
Pulmonary  arches,  296 

arteries,  296 

plexus,  304 

veins,  297 

Pulp  of  teeth,  99,  no 
Pupil,  dilatator  muscle  of,  456 

sphincter  muscle  of,  455 
Pupillary  membrane,  441 
Purkinje's  cells,  429 

fibers,  181 

Pycnotic  nuclei,  10,  189 
Pyloric  glands,  256 
Pulorus,  251 
Pyramidal  cells,  431 

tracts,  425 
Pyramids  of  Ferrein  (in  the  kidney),  315 

of  Malpighi  (in  the  kidney),  314 

of  the  medulla  oblongata,  424 


Rabl,  on  the  development  of  the  lens,  453 
Radial  fibers  of  the  retina,  447 
Rami  of  spinal  nerves,  136,  137 
Ranson,  on  ganglion  cells,  150 
Ranvier,  on  clasmatocytes,  71 

on  lymphatics,  184 

nodes  of,  144,  156 
Ranvier's  alcohol,  488 
Raphe  of  the  penis,  330 
Rathke,  on  gill  clefts,  219 

on  the  Wolffian  bodies,  327 
Rathke's  pouch,  435 
Reconstructions,  516 
Rectal  columns,  274 
Rectum,  247,  273 
Red  corpuscles,  188 

color,  1 88 

dimensions,  193 

number,  193 

shape,  191 
Red  nucleus,  425 
Reductional  division,  24 
Reflex  path  of  spinal  cord,  131 
Reflexa  (decidua  capsularis),  371 
Reissner's  membrane,  471 
Remak  on  nerves,  145 
Remak's  fibers,  145 
Renal  columns,  315 

corpuscles,  315 

lobules,  321 

papilla,  314 

pelvis,  322 

portal  system,  310 

pyramids,  314 

tubules,  312-316 
Resorcin-fuchsin,  504 
Respiratory  apparatus,  295 

bronchioles,  301 
Restiform  body,  423 
Resting  wandering  cells,  71 
Rete  Malpighii  (stratum  germinativum) ,  386 

ovarii,  351 

testis,  328,  339 


536 


INDEX 


Reticular  tissue,  62 
Reticulin,  62 
Retina,  443 

cones,  445 

development,  440 

fovea  centralis,  447 

macula  lutea,  447 

pars  ciliaris,  449 

pars  iridica,  455,  456 

par?  optica,  443 
.  pigment  layer,  440,  444 

rods,  444 
Retzius,  cells  of,  431 

lines  of,  105 

Reynolds,  on  ovulation,  357 
Rhinencephalon,  421 
Rhombencephalon,  422 
Rhomboidal  sinus,  37 
Richards,  on  mitosis,  14,  18,  19 
Rindfleisch,  on  red  corpuscles,  191 
Ringer's  solution,  488 
Riolanus,  ciliary  muscle  of,  462 
Rod  cells,  444 

Rollett,  on  muscle  striations,  123 
Rose,  on  tooth-development,  101 
Rosenmiiller,  fossa  of,  218 

organ  of  (epoophorori),  350 
Rouleaux,  191 
Round  ligament,  of  the  liver,  272 

of  the  uterus,  352 
Ruffini's  terminal  cylinders,  160 
Russel's  bodies,  in  plasma  cells,  70 
Ruysch,  on  epithelia,  46 


Sabin,  on  lymphatics,  184,  185 

lymph  glands,  224 
Sacculus,  467,  470 
Saccus  endolymphaticus,  465,  478 
Safranin,  502 
Salivary  corpuscles,  220 
Sappey,  on  lymphatics,  183 
Sarcolemma,  121 
Sarcomeres,  123 
Sarcoplasm,  124 
Sarcostyles,  120 
Scala  media  (cochlear  duct},  467,  471 

tympani,  468 

vestibuli,  468 
Schafer,  on  striated  muscle,  120,  122,  124 

non-medullated  nerve  fibers,  153 

development  of  blood  vessels,  166 

shape  of  red  corpuscles,  191 

blood  plates,  200 

sinusoids  of  the  liver,  287 

musculature  of  the  uterine  tube,  360 
Schaffer,  on  chordoid  tissue,  82 
Scharlach  R,  504 

Schlagenhaufen,  on  the  tactile  toruli,  385 
Schlemm,  canal  of  (sinus  venosus  solera},  460 
Schneider,  on  the  pituitary  gland,  430 
Schreger's  lines,  106,  109 
Schultze,  M.,  on  nerve  cells,  130 

white  corpuscles,  197 
Schultze,  O.,  on  muscle  and  tendon,  127 
Schulz,  on  bone,  92 
v.  Schumacher,  on  lamellar  corpuscles,  162 

haemolymph  glands,  210 


Schwann,  sheath  of,  144 

on  striated  muscle  fibers,  1 2 1 
Schweitzer,  on  the  lymphatics  of  the  teeth 

no 

Sclera,  456 
Sclerotome,  118 
Scrotum,  331 

Sebaceous  glands,  237,  397 
Secretion,  54 

internal,  58 

Secretory  capillaries,  57,  238 
Sections  (cutting  and  handling),  496 
Segmentation  of  the  ovum,  35 
Semicircular  canals  (ducts),  465,  470 
Seminal  vesicles,  329,  342 , 
Sensory  decussation,  426  ^ 

nerve  cells,  132,  134 

endings,  157 
Septa,  in  glands,  57 
Septula  testis,  332 
Septum  membranaceum,  177 

pellucidum,  421 

transversum,  276 
Serotina  (decidua  basalts},  371 
Serous  glands,  54.  237 
Sertoli's  cells,  of  the  testis,  335 
Serum,  201 
Sexual  cells,  20,  334 
Sharpey's  fibers,  92 
Sigmoid  colon,  247 
Silver  nitrate,  506 
Silvester,  on  lymphatics,  185 
Simple  epithelium,  48 
Sino-atrial  (or  sino-auricular)  node,  181 
Sinus,  coronary,  177 

lactiferous,  404 

rectalis,  274 

tonsillaris,  218 

transversus  pericardii,  175 

urogenital,  330,  353 

venosus,  177 
sclerse,  460 
Sinuses  of  the  dura  mater,  438 

in  lymph  glands,  205,  208 

in  haemolymph  glands,  209 
Sinusoids,  166 
Skin,  384 

corium,  384,  385 

epidermis,  384,  386 

hair,  389 

nails,  388 

sebaceous  glands,  397 

sweat  glands,  398 

vessels  and  nerves,  399 
Slides  and  cover  glasses,  508 
Small  intestine,  246 

blood  vessels,  266 

distention  of,  262 

duodenum,  246 

glands,  262 

ileum,  246 

jejunum,  246 

lymphatics,  267 

mesentery,  269 

nerves,  269 

villi,  262 

Smreker,  on  enamel  prisms,  107 
Sobotta,  on  fertilization,  33 
Solar  plexus,  139 


INDEX 


537 


Solitary  nodules,  207 
Somatopleure,  36 
Spermatic  cord,  342 
Spermatid,  22,  26,  336 
Spermatocytes,  22,  26,  336 
Spermatogenesis,  21 
Spermatogonia,  22,  23,  334 
Spermatozoa,  22,  26,  337 

discovery  of,  338 

number  in  man,  29 
Spermid,  22 
Spermium,  22 
Sphincter  pylori,  257 
Spinal  cord,  409 

central  canal,  409 

columns,  411 

commissures,  411 

dorsal  nucleus,  417 

ependyma,  418 

fasciculi,  411 

funiculi,  411 

gray  substance,  416 

horns,  411 

membranes,  413 

white  substance,  414 
Spinal  ganglia,  134 

nerves,  133 
Spindle,  17 

muscle- spindle,  159 
Spiracle,  216 
Spiral  ganglion,  476 

organ,  467,  472 
Spireme,  15 
Splanchnic  nerves,  138 
Splanchnopleure,  36 
Spleen,  210 

capsule,  214 

cells,  211,  213 

lobules,  215 

nodules,  211,  214 

pulp,  211,  213 
Spongioplasm,  4 
Squamous  cells,  49 
Stains,  general,  500 

selective,  503 
Staining  methods,  499 
Stapes,  469 

Steele,  on  intercalated  discs,  129 
Stenson's  duct  (parotid  duct},  238 
Stohr,  on  peripheral  nerves,  145 

thymus,  224 

glands  of  the  vermiform  process,  271 
Stomach,  246,  251 

glands,  253 

musculature,  257 

subdivisions,  251 
Stratified  epithelium,  48 
Streeter,  on  the  acoustic  nerve,  476 
Striated  muscle,  113,  128 
Stroma,  46 

Studnic'ka,  on  dentinal  fibers,  108 
Subarachnoid  space,  414,  439 
Subcardinal  veins,  309 
Subcutaneous  tissue  385 
Subdural  space,  413,  439 
Sublingual  glands,  242 
Sub  maxillary  glands,  242 
Substantia  adamantina,  99 

alba,  414 


Substantia  eburnea,  99 

gelatinosa,  417 

grisea,  416 

lentis,  452 

ossea,  99 

Sulphuric  acid,  489 
Supracardinal  vein,  310 
Suprarenal  gland,  404 
Supratonsillar  fossa,  218 
Sustentacular  cells,  of  the  inner  ear,  471,  475 

of  the  olfactory  epithelium,  484 

of  the  taste  buds,  235 

of  the  testis,  334 
Sweat  glands,  398 
Sylvius,  aqueduct  of,  422 
Sympathetic  ganglia,  137,  142,  150 

ganglionated  trunk,  138 

nervous  system,  137,  139 
Synapsis,  23 
Synarthrosis  96 
Synchondrosis,  91,  96 
Syncytium,  8 
Synizesis,  23 
Synovia,  99 
Synovia!  membrane,  98 


Tactile  cells,  157 

menisci,  158 
Taeniae  coli,  273 
Tapetum  cellulosum,  454 

fibrosum,  454 
Tarsal  glands,  462 
Taste  buds,  232,  234 

cells,  235 

Technique,  microscopical,  487 
Teeth,  99 

cement,  99,  in 

dentine,  99,  109 

enamel,  99,  104 

pulp,  99,  no 
Tela  submucosa,  220,  248 
Telencephalon,  419 
Tendon,  75 

spindles,  159 
Tenon's  capsule,  460 
Terminal  bars,  52 
Testis,  332 

cells,  332,  334 

convoluted  tubules,  334 

descent  of,  331 

development,  328 

interstitial  cells,  332 

muliebris,  365 

rete,  328,  339 

vessels  and  nerves,  333 
Tetrads,  23 
Thalamus,  421 
Thebesius,  veins  of,  179 
Theca  folliculi,  355 
Thoma,  on  the  development  of  blood  vessels, 

166 

Thoracic  duct,  183 
Thrombocytes,  199 
Thymus,  213,  222 
Thymic  corpuscles,  225 
Thyreo-glossal  duct,  217 
Thyreoid  gland,  217,  226 


538 


INDEX 


Tilney,  on  the  hypophysis,  43  7 

Tissues,  35 

Toldt,  on  gastric  glands,  253 

paradidymis,  344 
Tomes's  fibers,  107 

processes,  104 
Tongue,  230 
Tonsils,  lingual,  218,  222 

palatine,  218,  219 

pharyngeal,  218,  222 
Top-plate,  50 
Toruli  tactiles,  385 
Trabeculae,  205 
Trachea,  209 

Tradescantia,  cell  division  in,  14 
Transitional  epithelium,  324 

leucocytes,  196 

Triangular  ligaments  of  the  liver,i  278 
Tricuspid  valve,  177 
Trigeminal  nerve,  141,  423,  426 
Trochlear  nerve,  141,422 
Trophoblast,  367 
Trophoderm,  367 
Trophospongium,  5 
Tuberculum  impar,  230 
Tunica  albuginea,  327,  349  353 

propria,  220 
Tympanic  cavity,  470,  478 

membrane,  469,  480 
Tyson's  glands,  398 


U 


Umbilical  arteries,  381 

cord,  369,  380 

veins  279,  381 
Unipolar  cells,  143 
Units,  structurla,  of  kidney,  321 

of  the  liver,  284 

of  the  spleen,  215 
Unna,  on  plasma  cells,  70 
Urachus,  382 
Ureter,  311,  322 
Urethra,  female,  325 

male,  346 

Urinary  organs,  306 
Uriniferous  tubules,  313 
Urogenital  sinus,  330,  353 
Uterine  tubes,  327,  358 
Uterus,  327,  360 

masculinus,  346 

menstruating,  363 

pregnant,  366 
Utriculus,  466,  470 

prostaticus,  346 


Vacuoles,  4 
Vagina,  327,  383 

masculina,  346 
Vagus  nerve,  142,  424,  426 
Vallate  papillae,  230,  231 
Valves,  of  the  colon,  261,  273 

of  the  heart,  176 

of  Houston,  273 

of  lymphatic  vessels,  188 

of  the  veins,  164,  174 
Valvulae  conniventes  (circular  folds},  261 


Vas  deferens  (ductus  defer  ens},  324,  342 
Vasa  aberrantia  of  the  liver,  280 
Vasa  vasorum,  171 
Vascular  tissue,  44,  163 
Veins,  172 

Carolina!,  309 

portal,  277,  278 

pulmonary,  297 

umbilical,  279,  381 

vitelline,  44,  278,  279 
Vena  cava  inferior,  177,  279 
Venae  minimae,  179 
Ventral  aorta,  165 
Ventricles,  of  the  brain,  419,  421,  424 

of  the  heart,  175 
Vermiform  process,  270 
Vesalius,  on  blood  vessels,  164 

pituitary  gland,  436 
Vesica  fellea,  277 
Vesicular  follicles  of  the  ovary,  354 

supporting  tissue,  82 
Vestibule,  of  the  labyrinth,  468 

of  the  nose,  482 

of  the  vagina,  353 
Vibrissae,  482 
Villi,  amniotic,  382 

chorionic,  375 

intestinal,  260 

pleural,  306 

synovial,  98 
Visual  cells,  444 

purple,  444 
Vitelline  duct,  245 

veins,  44,  278,  279 
Vitreous  body,  442,  453 

humor,  442 
Volkmann's  canals,  93 
Vomero-nasal  organ,  141,  483 

W 

Waldeyer,  on  spermatozoa,  29 

oogenesis,  34 

plasma  cells,  68 
Wax  reconstructions,  516 
Weidenreich,  on  pigment  cells,  72 

shape  of  red  corpuscles,  191 

white  corpuscles,  195 

eosinophiles,  198 

the  spleen,  212 
Weigert's  iron  haematoxylin,  502 

method  for  myelin  sheaths,  510 

resorcin-fuchsin,  504 
Wepfer,  on  the  lobules  of  the  liver,  281 
Wharton,  on  the  suprarenal  glands,  405 
Wharton's  duct  (submaxillary  duct},' '242 

jelly,  62 

Whipple,  on  the  tactile  toruli,  385 
White  corpuscles,  188,  195 

fibers,  62 

nerves,  153 

rami,  137 

substance  of  the  spinal  cord,  414 
Wiesel,  on  the  suprarenal  gland,  406 
Williams,  L.  W.,  on  the  notochord,  38,  82 

somites  of  the  chick,  118 
Williams,  S.  R.,  on  anomalous  vessels,  166 
Willis,  on  the  intercostal  nerve,  136 

stomach,  251 


INDEX 


539 


Wilson,  on  fourth  molars,  101 

Wilson,  E.  B.,  on  sex  chromosomes,  21,  28 

Winslow,  foramen  of,  280 

Wolff,  on  the  kidney  (Wolffian  body),  306 

epigenesis,  339 
Wolffian  body,  306,  307 

duct,  41,  306,  307 

tubules,  308 

Wright,  on  blood  plates,  200 
Wright's  blood  stain,  505 

method  for  frozen  sections,  498 


X 


Xylol,  507 


Yolk  nucleus,  29 
sac,  39,  382 
stalk,  382 


Zenker's  fluid,  492 
Zona  columnaris,  247 

pellucida,  29 

radiata,  29 
Zonula  ciliaris,  449 
Zuckerkandl,  on  chromaffin  bodies,  152 

suprarenal  glands,  406 

organs  of  Zuckerkandl,  152 
Zymogen  granules,  255 


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